FISH

SMALL SUPERNUMERARY MARKER CHROMOSOMES

- sSMC 14 -

           References

In general 70% of sSMC carriers are clinically normal. The figures here
are based on the bias, that mainly clinically aberrant cases are reported in literature!

UPD (uniparental disomy) cases:           UPD 14   maternal   paternal   unclear


the probably non-dosage sensitive pericentric region of chromosome 14

 


SCHEMATIC CYTOGENETIC DEPICTION                    
  sSMC-14DISCLAIMER

 


 

SCHEMATIC MOLECULARGENETIC DEPICTION  


acc. to UCSC Genome Browser on Human Mar. 2006 assembly [UCSC hg18, 2006]
and available BAC-data/ array-data from cases marked *** mentioned below [MB]

 [p-tel ---   centromere 19.10]   uncritical region 20.24 --- 20.17 critical region

Below adapted for UCSC hg19, 2009

 [p-tel ---   centromere 19.10]   uncritical region 20.24 --- 20.97 critical region

 DISCLAIMER

 


 Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

14q - proximal

symptoms

 brain malformations

18 %

developmental delay

27 %

dysmorphic face

73 %

finger or toe/foot malformations

27 %

genital abnormalities

9 %

growth retardation

45 %

hearing problems/ loss

9 %

heart defect

9 %

hip problems

9 %

hypotonia

18 %

mental retardation

36 %

microcephaly

9 %

seizures

9 %

scoliosis

9 %

vision impaired

9 %
number of cases (marked with “°” below) 11

 



References

Cases without clinical findings (O)

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  14-O-
q1?0/
1-1
male/
1m
PBL maternal  47,XY,+mar[19]/
46,XY[81]
min(14)(pterq1?0)* all available centromeric probes normal at age of 11y  {9} case 28239   
  14-O-
q1?0/
1-2
male/
1m
PBL de novo 47,XY,+mar[~50%]/
46,XY[~50%]
min(14)(pterq1?0)* all available centromeric probes normal at age of  6y {9} case 41934  
  14-O-
q10/
1-1
male/
prenatal
AF de novo 47,XY,+mar[10] inv dup(14)(q10) cenM; subcenM see below {1} case 20  
Amniocentesis due to advanced  maternal age; no ultrasound abnormalities; child born without clinical symptoms
  14-O-
q10/
1-2
male/
27y
PBL de novo 47,XY,+mar[15] inv dup(14)(q10) acro-cenM; subcenM detected during  ICSI course; no clinical symptoms {31} case 14-42
{45} case 25
 
  14-O-
q10/
1-3
male/
28y
PBL n.a. 47,XY,+mar[15] inv dup(14)(q10) acro-cenM; subcenM detected during  ICSI course; no clinical symptoms apart from OAT 3. Grade {31} case 14-43
{45} case 26
 
  14-O-
q10/
1-4
male/
34y
PBL n.a. 47,XY,+mar[15] inv dup(14)(q10) acro-cenM detected during  ICSI course; no clinical symptoms apart from OAT syndrome {31} case 14-44
{45} case 27
 
  14-O-
q10/
1-5
male/
38y
PBL n.a. 47,XY,+mar[15] inv dup(14)(q10) acro-cenM see below {31} case 14-45  
detected due to prenatal diagnosis of child of female partner; no clinical symptoms in 38 year old male
  14-O-
q10/
1-6
female/
1m
PBL maternal 47,XX,+mar[100%] inv dup(14)(q10)* all available centromeric probes normal at age of  21y {9} case 40  
  14-O-
q10/
1-7
male/
prenatal
AF de novo 47,XY,+mar[17]/
46,XY[3]
inv dup(14)(q10)* all available acrocentric centromeric probes normal at age of  9 y {9} case 32830  
  14-O-
q10/
1-8
male/
1m
PBL paternal 47,XY,+mar[100%] inv dup(14)(q10)* all available centromeric probes normal pregnancy up to week 24; then preterm spontaneous birth with postnatal complications; normal at age of  9m {10} case 1  
  14-O-
q10/
1-9 to
1-12
female/
prenatal
AF paternal/
maternal/
de novo/ n.a.
47,XX,+mar[100%] 2x
[30%] 1x ({12}case6)
[20%] 1x ({12}case7)
inv dup(14)(q10)* all available centromeric probes Amniocentesis due to advanced  maternal age; no ultrasoundabnormalities; child born without clinical symptoms {12} cases 4-7  
  14-O-
q10/
1-13
male/
26y
PBL n.a. 47,XY,+mar[100%]  inv dup(14)(q10)* centromeric probes normal but infertility in partnership; severe oligoasthenospermia {18} case 1
{45} case 28
 
  14-O-
q10/
1-14
male/
adult
PBL n.a. 47,XY,+mar[15]  inv dup(14)(q10) cenM; 
subcenM
normal but fertility-problems in partnership {31} case 14-414
{45} case 29
 
  14-O-
q10/
1-15
female/
adult
PBL n.a. 47,XX,+mar[15]  inv dup(14)(q10) cenM; 
subcenM
normal; daughter with sSMC and abnormalities of unclear origin; no UPD 14 {31} case 14-415  
  14-O-
q10/
1-16
female/
38y
PBL n.a. 47,XX,+mar[100%] inv dup(14)(q10) centromeric probes;
subcenM
normal; daughter with same marker in 100% of the cells and dwarfism; suspicion of Turner syndrome {31} case 14-416  
  14-O-
q10/
2-1
see 13/21-O-q10/4-1 {14} case 26
{45} case 107
 
  14-O-
q11/
1-1
male/
prenatal
AF maternal
(age 34y)
47,XY,+mar[15] inv dup(14)(q11) acro-cenM; UPD-test Amniocentesis due to psychological indication age; no ultrasound abnormalities; child born without clinical symptoms; mother normal {3} case 3  
  14-O-
q11/
1-2
female/
28y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[50%]/
46,XX[50%]
inv dup(14)(q11) acro-cenM;
subcenM
normal female {31} case 14-6  
  14-O-
q11/
2-1
female/
18y
PBL n.a. 47,XX,+mar[100] min(14)(:p11q11:) cep probes studied due to a son with karyotype 47,XY,rob(13;21)(q10;q10),+21,+mar*  {64} mother of index case  
  14-O-
q11.1/
1-1
female/
37y
PBL n.a. 47,XX,+mar[43]/
46,XX[7]
inv dup(14)(q11.1) acro-cenM; subcenM; UPD-test detected during  ICSI course; no clinical symptoms {31} case 14-7
{45} case 30
 
  14-O-
q11.1/
1-2
female/
38y
PBL n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) acro-cenM Fertility problems; no other clinical symptoms {31} case 14-8
{45} case 31
 
  14-O-
q11.1/
1-3
male/
36y
PBL n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) cenM; subcenM Fertility problems; OAT-syndrome; no other clinical symptoms {45} case 32  
  14-O-
q11.1/
1-4
male/
prenatal
AF de novo 47,XY,+mar[100%] inv dup(14)(q11.1) centromeric probes; subcenM; UPD-test detected due to advanced  maternal age; baby normal in ultrasound, born normal with 3210 g, APGAR 8/9 {0} provided by UNIQUE  
  14-O-
q11.1/
1-5
male/
prenatal
AF ? de novo 48,XXX,+mar[8]/
47,XXX[44]
inv dup(14)(q11.1) acro-cenM, subcenM; UPD-test Advanced maternal age; child born and normal {0} provided by Dr. Mazauric, Düsseldorf, Germany  
  14-O-
q11.1/
1-6
male/
39y
PBL n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) acro-cenM, subcenM ICSI patient; normal male {0;45} case 33  
  14-O-
q11.1/
1-7
female/
25y
PBL paternal 47,XX,+mar[100%] inv dup(14)(q11.1) centromeric probes, subcenM normal female; father normal as well {0} provided by Dr. Pabst, Hannover, Germany  
  14-O-
q11.1/
1-8
male/
adult
PBL n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) cenM, subcenM normal male; repeated abortions in his wife {45} case 34
{47} case 8
 
  14-O-
q11.1/
1-9
female/
32y
PBL n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) acrocenM, subcenM normal female; prenatally detected child with same marker - thus, cytogenetics done in mother as well {0}provided by Hanne Tittelbach, Nürnberg, Germany  
  14-O-
q11.1/
1-10
female/
29y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[52%]
46,XX[48%]
inv dup(14)(q11.1) cenM, subcenM normal female; repeated abortions {39} case 6
{45} case 35
 
  14-O-
q11.1/
1-11
male/
45y
PBL
(EKF-
cellbank)
n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) cenM, subcenM normal male;  unfulfilled wish for children {45} case 36  
  14-O-
q11.1/
1-12
female/
adult
PBL n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) acrocenM, subcenM normal female {47}case 9  
  14-O-
q11.1/
1-13
female/
adult
PBL n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) acrocenM, subcenM normal female;  mar detected as mar also present in unborn child. {47}case 10  
  14-O-
q11.1/
1-14
female/
27y
PBL
(EKF-
cellbank)
paternal 47,XX,+mar[100%] inv dup(14)(q11.1) cep probes subcenM normal female, father normal as well; sSMC detected due to abortus {0}  
  14-O-
q11.1/
1-15
male/
prenatal
AF maternal 47,XY,+mar[100%] inv dup(14)(q11.1) cep probes subcenM pregnancy outcome unknown; mother normal {0}  provided by Dr. Fuchs, Hamburg, Germany  
  14-O-
q11.1/
1-16
male/
adult
PBL n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) cep probes subcenM normal male with severe type of oligospermia {0} provided by Dr. Ma Sai (Vancouver, Canada)  
  14-O-
q11.1/
1-17
male/
35y
PBL n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) cep probes subcenM normal male, infertile {0} provided by Jasen Anderson, Brisbane, Australia  
  14-O-
q11.1/
1-18
female/
prenatal
AF de novo 47,XX,+mar[100%] inv dup(14)(q11.1) cep probes subcenM; UPD-test normal child born {58} case 19  
  14-O-
q11.1/
1-19
female/
63y
PBL n.a. 47,XX,inv(19)(p13.3q13.1),
+mar[100%]
inv dup(14)(q11.1) cenM; subcenM normal female; reason for cytogenetic analysis unknown {0} provided by Jasen Anderson, Brisbane, Australia  
  14-O-
q11.1/
1-20
female/
prenatal
AF maternal 47,XX,+mar[100%] inv dup(14)(q11.1) cenM; subcenM mother normal female;  normal child born {0} provided by Dr. Engels, Bonn, Germany  
  14-O-
q11.1/
1-21
male/
prenatal
AF de novo 47,XY,+mar[100%] inv dup(14)(q11.1) cenM; subcenM; UPD-test advanced maternal age, normal child born {58} case 20  
  14-O-
q11.1/
1-22
male/
prenatal
AF de novo 47,XY,+mar[96%]
46,XY[4%]
inv dup(14)(q11.1) cenM; subcenM; UPD-test advanced maternal age, normal child born {0} provided by Dr. Dufke, Tübingen, Germany  
  14-O-
q11.1/
1-23
n.a./
prenatal
AF/ PBL de novo 47,+mar[88%]
in PBL 87%
inv dup(14)(q11.1) midi twin pregnancy; mar only in one twin,  normal child born {49}case 1  
  14-O-
q11.1/
1-24
male/
prenatal
AF n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) cenM; subcenM; UPD-test studied due to sonographic markers: white spot, pericardia effusion; also previous  anti-sterility treatment; normal child born {0} provided by Dr. Kistner, Schwerin, Germany  
  14-O-
q11.1/
1-25
female/
prenatal
AF de novo 47,XX,+mar[100%] inv dup(14)(q11.1) cenM; subcenM; UPD-test advanced maternal age; normal child born, normal at 1 years of age {56}  
  14-O-
q11.1/
1-26
female/
prenatal
AF de novo 47,XX,+mar[100%] inv dup(14)(q11.1) cenM; subcenM advanced maternal age; normal child born, normal at 0.5 years of age {0} provided by Dr. Henderson, Bloemfontein, South Africa  
  14-O-
q11.1/
1-27
female/
32y
AF n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) cenM; subcenM normal female; reason for cytogenetics not known {0} provided by Dr. Polityko Minsk, Belarus  
  14-O-
q11.1/
1-28
male/
prenatal
AF maternal 47,XY,+mar[100%] inv dup(14)(q11.1) cenM; subcenM; UPD-test advanced maternal age, normal child born, mother normal {58} case 21  
  14-O-
q11.1/
1-29
male/
33y
PBL
(EKF-
cellbank)
n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) cenM; subcenM normal male, fertility problems {0}  
  14-O-
q11.1/
1-30
female/
prenatal
PBL
(EKF-
cellbank)
maternal 47,XX,+mar[100%] inv dup(14)(q11.1) cenM; subcenM prenatally detected by chance, mother normal {0} provided by Dr. Behrend, Düsseldorf, Germany  
  14-O-
q11.1/
1-31
female/
36y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[7]/
46,XX[23]
inv dup(14)(q11.1) cenM; subcenM normal female, infertile {0} provided by Dr. Morlot, Hannover, Germany  
  14-O-
q11.1/
1-32
female/
29y
PBL n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) cenM; subcenM normal female, infertile {0} provided by Dr. Duba, Linz, Austria  
  14-O-
q11.1/
1-33
male/
prenatal
AF n.a. 47,XY,+mar[61%]/
46,XY[39%]
inv dup(14)(q11.1) cenM; subcenM normal male born and normal at 6 months {0} provided by Dr. Manolakos, Athens, Greece  
  14-O-
q11.1/
1-34
female/
prenatal
AF n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) cenM; subcenM normal female born and normal at 3 months {0} provided by Dr. Manolakos, Athens, Greece  
  14-O-
q11.1/
2-1
male/
prenatal
CH; umbilical chord blood de novo CH: 47,XY,+mar[50%]/
46,XY[50%]
UBL: 48,XY,+marx2[2%]/
47,XY+mar[12]/
46,XY[3]
inv dup(14)(q11.1)(x2) centromeric probes,  subcenM; UPD-test Chorion biopsy due to advanced maternal age and enhanced nuchal translucency in early pregnancy; normal child born with weight 3920g and length 52cm; APGAR 8/9/9; {0} provided by Dr. Wiedemann, Bern, Switzerland  
  14-O-
q11.1/
2-2
female/
40y
PBL n.a. 48,XX,+2mar[100%] inv dup(14)(q11.1)(x2) cenM;  subcenM normal female, fertility problems {45} case 37  
  14-O-
q11.1/
3-1
female/
40y
PBL n.a. 47,XX,+mar[15%]/
46,XX[85%]
r(14)(::p1?2q11.1::) cenM;  subcenM; UPD-test normal female born studied prenatally due to advanced maternal age {0} provided by Dr. Apeshiotis, Braunschweig, Germany  
  14-O-
q11.1/
4-1
female/
prenatal
AF de novo 47,XX,+mar[100%] min(14)(:p11.1q11.1::) cenM;  subcenM normal female born (normal at 6m) studied prenatally due to advanced maternal age {0} provided by Dr. Lemmens, Aachen, Germany  
  14-O-
q11.1/
4-2
male/
prenatal
AF n.a. 47,XY,+mar[100%] min(14)(pterq11.1:)  ceps;  subcenM Amniocentesis due to advanced  maternal age; normal child born; normal at 3 y {70} case Sm-6  
  14-O-
q11.2/
1-1
male/
prenatal
AF; PBL de novo 47,XY,+mar[100%] dic(14;15)(14pter14q11.2:
:15q11.1
15pter)
cep 14/22; cep 15; cep 13/21 characterization of #14 by p-arm polymorphism analysis Amniocentesis due to advanced  maternal age; no ultrasound abnormalities; normal child born at term {11} case 2; {73}
 
  14-O-
q11.2/
2-1
male/
prenatal
AF n.a. 47,XY+mar[15]/
46,XY[10]
dic(14)(:p11.1q11.1: :p11.1q11.2:)
BAC RP11-324B11 in 14q11.2 present once (19.88MB)
M-FISH
subcenM-FISH
Amniocentesis due to advanced  maternal age; normal child born {0} provided by Dr. U. Trautmann,
Erlangen, Germany
 
  14-O-
q11.2/
3-1
female/
29y
PBL n.a. 47,XX,+mar[40]/
46,XX[60]
min(14)(pterq11.2:)
BAC RP11-324B11 in 14q11.2 present once (19.88MB)
acrocenM
subcenM-FISH
normal female, fertility problems {45} case 38  
  14-O-
q11.2/
4-1
male/
32y
PBL n.a. 47,XY,+mar[100%] r(14)(::p11.2q11.2::) n.a. normal male, fertility problems - oligospermia {42}  
  ***
14-O-
q11.2/
5-1
***
male/
prenatal
AF maternal
(in PBL sSMC 100%)
47,XY,+mar[100%] inv dup(14)(q11.2)
BAC
RP11-324B11 in 14q11.2 present twice (19.88MB)
array: 18.45-20.24
acrocenM
subcenM-;
aCGH
advanced maternal age; pregnancy outcome unknown but mother clinically normal {70}  case Si-1  
  14-O-
q11.2/
5-2
male/
prenatal
AF maternal 47,XY,+mar[100%] inv dup(14)(q11.2) MLPA abnormal first trimester screening; mother normal {59} case 10  
                     

 

 

O-cases with unclear/insufficient characterization of the sSMC itself (CO)

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  14-
CO-1
female/
prenatal
AF maternal 47,XX,+mar[?] mar(14) different FISH probes (D14/22Z1; wcp14) Amniocentesis due to advanced  maternal age;  child normal at birth {6} case 10
{7} case 17
 
  14-
CO-2
female/
prenatal
AF/PBL de novo 47,XX,+r[7]/
46,XX[14]
(in PBL after birth mar in 6/20 cells)
r(14) SKY; cep14/22 telomeric and sub-telomeric probe Amniocentesis due to advanced  maternal age; birth at term, no clinical signs at birth and at 6m; however infantile spasms at 6m, which could be treated {15}  
  14-
CO-3
male/
postnatal, adult
PBL n.a. 48,XY,+marx2[100%] mar(14) centromeric probes child of normal person mentioned here with DMD studied cytogenetically; 47,XX,+mar was detected; two mar present in father {20} case 12  
  14-
CO-4
male/
1y
PBL
cell line at ECACC DD0618
de novo 47,XY,+mar[?]/
46,XY[?]
mar(14) n.a.; UPD-test clinically normal {5} case 12  
  14-
CO-5
female/
32y
PBL
cell line at ECACC DD1233
maternal 47,XX,+mar[57%]/
46,XX[43%]
mar(14) n.a.; UPD-test clinically normal; daughter with same marker {5} case 14  
  14-
CO-6
female/
prenatal
AF maternal 47,XX,+mar[100%] mar(14) cep probes clinically normal {13} case17  
  14-
CO-7
male/
prenatal
AF maternal 47,XY,+mar[100%] mar(14) cep probes clinically normal {13} case 18  
  14-
CO-8
male/
postnatal
PBL maternal 47,XY,+mar[100%] mar(14) cep probes mother and child clinically more or less normal {13} case 18  
  14-
CO-9
n.a./
postnatal
PBL n.a. 47,+mar[100%] mar(14) cep probes normal {14} case 15  
  14-
CO-10
female/
adult
PBL n.a. 47,XX,+mar[100%] mar(14) cep probes normal with poor reproductive history {14} case 16
{45} case 40
 
  14-
CO-11
female/
adult
PBL de novo 47,XX,+mar[100%] mar(14) cep probes normal with primary amenorrhea {20} case 10
{45} case 41
 
  14-
CO-12
male/
prenatal
PBL paternal 47,XY,+mar[?]/
46,XY[?]
mar(14) cep probes normal father with 100% sSMC, child with sSMC abnormal {20} father of case 14  
  14-
CO-13
to 17
n.a./
prenatal
AF 2x maternal; 3x de novo 47,+mar[?%] inv dup(14) n.a. normal mother and/ or normal ultrasound {57} 5 cases  
  14-
CO-18
female/
30y
PBL n.a. 47,XX,+mar[100%] mar(14) M-FISH; wcp 14 normal female with fertility problems; one pregnancy (TOP) with congenital malformations; female herself with polycystic ovaries and irregular menstrual cycle {0} provided by Dr. Hema Purandarey, Piramal Diagnostics, Center for Genetic Health Care, Mumbai with acknowledgement to Dr. Sonal R. Bakshi, Institute of Science, Nirma University, Ahmedabad  
  14-
CO-19
female/
prenatal
AF n.a. 47,XX,+mar[100%] mar(14) wcp 14, cep 14/22 AMA, normal child born {71} case 27  
                     

 

 

 


References

Cases with clinical findings (W)

  

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  14-W-
q10/
1-1
female/
prenatal
AF n.a. 47,XX,+mar[95%]/
46,XY[5%]
inv dup(14)(q10) midi, subcenM see below {0}  provided by Dr. N. Rubtsov, Novosibirsk, Russian Federation  
upward slant of palpebral fissures, tall stature, asthenic type, arachnodactyly, hyperextension of ulnar, radius and interphalangeal joints, asymmetric thorax, pectus excavatum, scoliosis, additional chord of the left ventricle, prolapse of the mitral valve, tachycardia, nephroptosis, spontaneously aborted.
  14-W-
q10/
1-2
female/
prenatal
AF n.a. 47,XX,+mar[%?] inv dup(14)(q10) midi, subcenM see below {0}  provided by Dr. N. Rubtsov, Novosibirsk, Russian Federation  
Up-slanting palpebral fissures, prominent premaxillary, malocclusion, micrognathia/ retrognathia, high vaulted and narrow palate, hyperthelia, additional chord of the leftventricle, excessive pilosis, pollex hypermobility. Pregnancy was aborted.
  14-W-
q11.1/
1-1
female/
adult
bone marrow de novo acquired case 1: 48,XX,+4,+18,-19,-21,-22,+3mar, t(3;10)(q11;q12),t(12;14)(q24;q11)
case 2: 46,X,-X,-10,-12,+14,-17,+3mar,t(14;14)(q11;q32)
n.a. see below {30}  cases 2 and 4  
hint on repeated involvement of the breakpoint 14q11 in cases with adult T-cell leukemia; involved is T-cell receptor gene
  14-W-
q11.1/
2-1
moved to 14-U-14 {41}  
  14-W-
q11.1/
3-1
moved to 14-U-15 {72}  
  14-W-
q11.1
~11.2/
1-1
moved to 14-U-16 {35} case 3; {0}  
  ***
14-W-
q11.2/
1-1 °
***
n.a./
postnatal
PBL n.a. 47,+mar[100%] min(14)(pterq11.2:)*
distal clone in 14q RP11-14J7 (20.17MB)
array-CGH see below {38}case 7  
dysmorphic features
  14-W-
q11.2/
2-1 °
male/
postnatal
PBL n.a. 47,XY,+mar[100%] r(14)(::p11.2q11.2::) CGH hypogonadotopic Hypogonadism, moderate mental developmental delay, precocious puberty, small hands, scoliosis {40} case 12  
  14-W-
q11.2/
2-2 °
male/
16y
PBL n.a. 47,XY,+mar[14]/
46,XY[16]
r(14)(::p11.?2q11.2::) cenM; subcenM normal apart from dwarphism {0} provided by J. Anderson, Brisbane, Australia  
  14-W-
q12/
1-1
male/
~1y
PBL de novo 47,XY,+mar[100%] min(14)(pterq12:)
13.43 MB of euchromatin
 SNP aCGH oligohydramnios at 24 weeks pregnancy,; at birth weight 2500 g (3rd centile), length 47 cm (10th centile), head circumference 34 cm (10th centile); at 7 months pneumonia and general muscular hypotonia, transverse palmar creases, hypogammaglobulinemia, facial dysmorphism; at 27 months, height 80 cm (1st centile), weight 12 kg (3rd centile), head circumference 48 cm (5th centile). Severe developmental delay and brain malformations, strabism  {74}  
  14-W-
q13.2/
1-1
moved to 14-U-32 {62}  
  14-W-
q13.3/
1-1
male/
8y
PBL de novo 47,XY,+mar[90%]/
46,XY[10%]
r(14)(::p11?.1q11.1:
:q13.3-q21.1::)[96%]/
r(14;14)(::p11?.1
q11.1: :q13.3-q21.1:
:p11?.1
q11.1:
:q13.3-q21.1::)[4%]
different FISH-probes: telomeric probe; all centromeric probes; UPD-test developmental delay; moderately retarded, hypotonia, speech delay, dribbling {8} case 5  
  14-W-
q13/
1-1  °
 
male/
prenatal
AF de novo 47,XY,+mar[100%] inv dup(14)(q13) different FISH-probes: wcp14, YACs as specified in {17} see below {17}  
Amniocentesis due to ultrasound abnormalities in week 18 and 23 (among others unilateral talipes); pregnancy terminated; autopsy revealed correct length and weight, but prominent nasal bridge, protuberant forehead, ears low set and posteriorly angulated, camptodactyly bilateral clinodactyly, shortening of talipes of left leg, brain with ventriculomegaly, possible delayed neuronal migration
  14-W-
q13/
1-2  °
 
male/
1m
PBL de novo 47,XY,+mar[16]/
46,XY[47]
at 2 years same rate of sSMC, at 7y 42% in PBL
in buccal mucosa stable at ~20%
inv dup(14)(q13.1)
size 14.5 MB
different FISH-probes: wcp14, BACs as specified in {28} see below {28; 63}  
The third boy of a healthy Turkish consanguineous couple was born at term after an uneventful pregnancy. Weight: 2,490 g (3rd centile), length 48 cm (10th centile), head circumference 34 cm (10th centile). Dysmorphism: craniofacial features like head asymmetry, high-arched eyebrows, epicanthal folds, broad and high nasal bridge, bulbous nasal tip, flared nostrils, protruding philtrum, thin lips, posteriorly rotated low-set ears, retrognathia, sparse hair, omphalocoele, abnormally widely placed nipples, bilateral coloboma of the iris. Left hand with a single palmar crease tracheomalacia→ stridor at age of 6 weeks. At age of 10 months marked psychomotor delay (DQ 30-50). And body measurements below the 3rd centile.
  14-W-
q13/
1-3  °
 
female/
prenatal
AF de novo 47,XX,+mar[100%] inv dup(14)(q13)  wcp14 see below {34}  
Amniocentesis due to advanced maternal age, a previous missed abortion and growth retardation with talipes varus at both feet in week 20. pregnancy terminated in week 22. Postmortem examination showed: prominent forehead, protruding philtrum, overlapping columella nasi, micrognathia and retrognathia, low-set and posteriorly rotated ears, bilateral talipes varus, camptodactyly, clinodactyly, large heavy maceration, high dilatation of first and second ventricles, bilobated lungs, visceral immaturity, generalized congestion after opening of cavities, below normal weight of 300g. placenta with micro calcifications, umbilical cord with only two vessels.
  14-W-
q13/
1-4  °
n.a./
few months
PBL de novo 47,+mar[?%] inv dup(14)(q13) n.a. see below {29; summary in 36}  
died at age of 11 months, mental retardation, pre- and postnatal growth retardation; microcephaly, low set malformed ears, cleft palate, flat facies, down slanting palpebral fissures, camptodactyly, hearing problem, blind, cardiovascular anomalies
  14-W-
q13/
2-1
female/
prenatal
AF de novo 47,XX,+mar[100%] min(14)(:q13q24.3:) wcp 14, D14/22Z1 see below {0}studied by Genzyme, USA  
sSMC detected prenatally due to ultrasound abnormalities and infection in amnion water - due to broken amniowall; TOP at 23rd week of gestation; weight 419g, discoid placenta, ventricular septal defect, acute chorioamnionitis; head circumference 18cm, chest circumference 15.2 cm, abdominal circumference 12.8cm, length ~26cm. slightly low set right ear, hypoplastic thymus; data included here according to wish and permission of parents.
  14-W-
q13/
3-1  °
female/
newborn
PBL n.a. 47,XX+mar[100%] min(14)(pterq13:) cenM, subcenM see below {0}provided by Dr. Emel Ergul, Turkey  
as newborn right leg turned inwards, facial dysmorphism, hypotonia
  14-W-
q13.3/
1-1 °
male/
17y
PBL de novo 47,XY,inv(9)(p12q13),+mar[40%]/
46,XY,inv(9)(p12q13)[60%]
r(14)(::p12q13.3::) cenM, subcenM; UPD-test see below {0}provided by Thomas Martin, Homburg, Germany  
mental retardation and facial dysmorphism
  14-W-
q21.2
1-1  °
 
n.a./
newborn
PBL de novo 48,+mar1,+mar2[35%]/
47,+mar1[65%]
min(14)(pterq21.1:)*
min(14)(q11.2)*
centromeric probes  wcp 14 see below {36}  
normal pregnancy; born by cesarean section at 39+2 weeks; APGAR 3, 7, 8. birth weight 2165g head circumference 32,2 cm, small low-set ears cleft palate, apparently small eyes with coloboma bilaterally and short palpebral fissures; right pelvic kidney, slightly distended ventricles; feeding problems in first months due to aspiration problems; at 7m developmental delay of 3m; hypotonia, bilateral hearing loss, severe multifocal epilepsy; at 1 m patient died as consequence of multiple cyanotic incidents due to convulsion and aspiration. no autopsy
  14-W-
q22
1-1  °
 
n.a./
prenatal
chord blood de novo 47,+mar[100%] min(14)(pterq22:)* centromeric probes  wcp 14 see below {32} case 12  
Amniocentesis due to abnormal ultrasound, and advanced maternal age; in US IUGR, polyhydramnion, corpus callosum agenesis, TOP - no further data available
  14-W-
q22
1-2 
 
female/
9m
PBL de novo 47,XX,+mar[100%] min(14)(pterq22:)* SKY
BACs
see below {74}  
global developmental delay, seizures, microcephaly, flat nasal bridge, epicanthal fold, CT --> frontal cerebral atrophy, hypsarrhthmia; Died at 4.5 years
                     

 

W-Cases with similar imbalances NOT caused by sSMC (W-IMB)

 

                   
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result and FISH result incl. grade of mosaicism test
methods
clinical symptoms reference  
  14-W-
IMB-
q13/
1-1 to
1-4
female and male/
postnatal
PBL maternal (balanced
translocations)
der(14)t(14;div. chrs.)(q13;div. breakpoints) n.a. see below {51-54}
reviewed in {50}
 
features in common: microcephaly, mental retardation, hypotelorism, strabismus, blepharophimosis, downturned corners of the mouth, small mandibles, low-set ears, short neck, sacral dimple
                   

 

W-cases with unclear/insufficient characterization of the sSMC itself (CW)

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  14-
CW-1
female/
7y
PBL
cell line at ECACC DD0922
de novo 47,XX,+mar[13]/
46,XX[87]
acc to {33} in cell line karyotype 47,XX,+2[25%]/46,XX[75%]
mar(14) all available centromeric probes;  UPD-test see below {5} case 13
{14} case 13
{33} case 19
 

mildly dysmorphic: frontal bossing, wide jaw, broad nasal bridge, slight down slating palpebral fissures, low anterior hairline, frontal cowlick, thick eyebrows, small ears, narrow palate; HC on 97th centile. Learning difficulties; analyzed due to suspicion of Noonan syndrome

  14-
CW-2
moved to 14-U-13 {35} case 7  
                     


CW-cases without extensive details on the cases (CWw)

 

         
  case no.  clinical symptoms reference  
  14-CWw-1 to 14-CWw-3 mentally retarded; min x1, inv dup x2

{14} cases 14;17-18

 
  14-CWw-4 abnormal phenotype; 1 min

{48}1 case

 
         

 


References

Cases with unclear clinical correlation (U)

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  14-
U-1
male/
prenatal
AF de novo 47,XY,+mar[5]/
46,XY[5]
inv dup(14)(q11) M-FISH; cenM see below {2} case 4
{4} case 4
 
Amniocentesis due to advanced  maternal age; white spot in left heart chamber, no further information available
  14-
U-1a
female/
prenatal
AF de novo 47,XY,+mar[9]/
46,XY[5]
inv dup(14)(q11.1) cenM; subcenM see below {2} case 1
{4} case 1
{0}
 
Amniocentesis due to advanced  maternal age; white spot in left heart chamber, no further information available
  14-
U-1b
female/
prenatal
AF de novo (?) 47,XX,t(9;14)(q22.1~q22.2;q21),
+mar[100%]
inv dup(14)(q11.1) cenM; subcenM Amniocentesis due to advanced  maternal age; normal(?) child born {0} provided by Dr. Wegner, Berlin, Germany  
  14-
U-1c
n.a./
prenatal
AF n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) ceps; subcenM Amniocentesis due to advanced  maternal age; no further info available {0} provided by Dr. Hörtnagel, Munich, Germany  
  14-
U-1d
female/
prenatal
AF n.a. 47,XX,+mar[28]/
46,XX[34]
inv dup(14)(q11.1) cenM;  subcenM; UPD-test advanced maternal age? - no info available {0} provided by Dr. Behrend, Düsseldorf, Germany  
  14-
U-1e
male/
prenatal
AF n.a. 47,XY,+mar[42]/
46,XY[34]
inv dup(14)(q11.1) cenM;  subcenM; UPD-test advanced maternal age? - no info available {0} provided by Dr. Tittelbach, Nürnberg, Germany  
  14-
U-1f
male/
prenatal
AF n.a. 47,XY,+mar[100%] inv dup(14)(q11.1) cenM; subcenM no info available {0} provided by Carme Fuster, Barcelona, Spain  
  14-
U-2
female/
1y
PBL de novo 47,XY,+mar[15] min(14)(:p12q11.1:)  M-FISH;
cenM
subcenM; UPD-test
possible problems perinatally; dystrophy; length and weight at 1y < 3. Percentile plus microcephalus; the latter not present at birth; extreme feeding problems {0} provided by Dr. C. Löffler, Chemnitz, Germany  
  14-
U-2a
male/
postnatal
PBL n.a. 47,XY,+mar[50%]/
46,XY[50%]
min(14)(:p12q11.1:) cep probes, subcenM n.a. {0} provided by Dr. Binkert, Düdingen, Switzerland  
  14-U-2b female/
10y
PBL de novo 46,X,+mar[100%] min(14)(pterq11.1:) cenM;  subcenM Turner Syndrome, short stature, webbing of neck, cubitus valgus, shield chest {60}case P-7
{61}
 
  14-
U-2c
male/
1y
PBL n.a. 47,XY,+mar[44]/
46,XY[6]
min(14)(pterq11.1:) cenM;  subcenM abnormal {0} provided by Dr. Polityko, Minsk, Belarus  
  14-
U-2d
moved to 14-O-q11.1/4-2    
  14-
U-2e
male/
prenatal
AF n.a. 47,XY,+mar[7]/
46,XY[17]
in interphase sSMC in 70%
min(14)(p11.1q11.1:) cenM; subcenM Amniocentesis due to advanced  maternal age; no further info available {0} provided by Dr. Hickmann, Düsseldorf, Germany  
  14-
U-3
male/
prenatal
AF de novo 47,XY,+mar[50%]/
46,XY[50%]
min(14)(:p11.1q11.1:)[7]/
inv dup(14(:p11.1
q11.1:
:q11.1
p11.1:)[4]
cenM; subcenM; UPD-test Amniocentesis due to advanced  maternal age; no further info available {0} provided by Drs. Wegner, Stumm, Berlin, Germany  
  14-
U-4
n.a./
n.a.
n.a. n.a. 47,+mar[?] ?min(14)  n.a. phenotype unknown {19} case 25
{46} case 31
 
  14-
U-5
female/
16y
PBL de novo 48,XXX,+mar[100%] min(14)(pterq21)  CGH see below {26}   
facial dysmorphism, high-pitched cry, severe developmental delay, developed an aggressive ovarian immature teratoma.  
  14-
U-6
male/
prenatal
AF
cell line at ECACC DD0357
de novo 47,XY,+mar[60%]/
46,XY[40%]
mar(14)  all centromeric probes; UPD-test pregnancy terminated; phenotype unknown {5} case 11
{16} case 8
 
  14-
U-7
n.a./
n.a.
n.a. n.a. 47,+mar[?%] mar(14) n.a. n.a. {37} 1 case  
  14-
U-8
to 10
2x female/ 1x male/
prenatal
AF de novo 47,+mar[?%]/
46[?%]
mar(14) cep probes TOP, normal at autopsy {20} cases 11, 13, 15  
  14-
U-11
n.a./
prenatal
AF maternal
t(3;14)
47,+mar[?%] der(14)t(3;14) n.a. TOP {57} 1 case; {73}
 
 
  14-
U-12
female/
postnatal
PBL n.a. 47,XX,+mar,16qh-[19]/
46,XX,16qh-[1]
der(14)t(5;14)(14pter14q13:
:5p13.3
5pter)
cenM;  subcenM; MCB Psychomotor delay, coloboma, cleft palate, agenesis of corpus callosum, dysmorphic ears, abnormal external genitalia, microcephaly. {72; 73}  
  14-
U-13
male/
prenatal
AF de novo 47,XY,+mar[100%] mar(14)
maternal UPD
n.a.;  UPD-test Amniocentesis due to advanced maternal age; normal child born; weight 2910g, length 51cm, OFC 34cm; no further information available {35} case 7  
  14-
U-14
female/
1y
PBL de novo 47,XX,+mar[44]/
46,XX[6]
inv dup(14)(q11)
paternal isoUPD 14
centromeric probes, subcenM; UPD-test see below {41}  
Patient born after a pregnancy complicated by severe polyhydramnion. No invasive prenatal diagnostics was done. Delivery was by Caesarean because of fetal distress at 37 weeks gestation. Birth weight 2,500 g (10th centile), OFC 34.8 cm (50th centile), and APGAR scores were 5 and 6 at 1 and 5 min, respectively. At birth profoundly hypotonic with reduced respiratory effort and required positive pressure ventilation. On examination, thorax small and bell shaped. Chest X-ray demonstrated lung hypoplasia, a ‘coat hanger’ shape of the ribs and elongated clavicles. There was stippled premature ossification of the proximal humeral epiphyses. She had a marked scoliosis convex to the  right. Palpebral fissures were short. There were contractures of the wrists with ulnar deviation bilaterally, second digit extensor contractures and swan neck deformity of third and fourth digits bilaterally. She had a prominent forehead with an elongated philtrum, a midline tubercle of the upper lip vermilion, and a broad flat nasal bridge with anteverted nares. She had an H-shaped pattern of creases under the lower lips reminiscent of the Freeman-Sheldon syndrome. Skull X-ray revealed a hypoplastic maxilla and mandible and a small anterior fossa. There was diastasis of the recti and significant hepatomegaly. She developed severe pulmonary hypertension with right heart enlargement and a large patent ductus on day 2 of life, required continuous positive airways pressure until day 43 and had supplemental oxygen therapy after discharge at a variable flow of 100-250 ml/min. She required nasogastric tube feeding due to a poor swallowing reflex and inadequate airway protection, and regular oropharyngeal suction was necessary. She developed recurrent episodes of pneumonia and died of respiratory failure secondary to a respiratory infection at age 5 months. Autopsy demonstrated architecturally and cytological normal skeletal muscle, skin, liver, and nerves.
  14-
U-15
male/
31y
PBL
(EKF-
cellbank)
de novo 47,XY,+mar[26]/ 46,XY[4] min(14)(pterq11.1:)
maternal UPD 14
acrocenM, subcenM; UPD-test male with short stature and adipositas {72}  
  14-
U-16
male/
prenatal
AF and PBL de novo 47,XY,+mar[100%] min(14)(pterq11.1~q11.2:)
maternal UPD 14
different FISH-probes: subcenM; UPD-test see below {35} case 3; {0}  
Amniocentesis due to abnormal triple test; child born in week 29 - birth weight 950g (10.th centile), length 37 cm (25th centile), OFC 26.3 (25th centile), APGAR 7/7; hypotonia up to 18 months of age-developmental delay; no mental retardation; at 4y all values <3rd centile (height 85cm, weight 11.5 kg, OFC 47,5 cm); microcephaly, simian crease, developmental delay, small stature, hypotonic
  14-
U-17
female/
prenatal
AF n.a. 47,XX,+mar[100%] der(14)t(14;16)
(q12;q21)
MLPA; BACs and cep pes equinovarus bilateral, overlapping fingers, intrauterine growth retardation {59} case 11; {73}
 
 
  14-
U-18
male/
5y
PBL maternal
t(14;17)
47,XY,+mar[100%] der(14)t(14;17)(q11.2;q25.3) subcenM body and facial dysmorphy, arachnoid cyst behind cerebellum, pineal gland cysts, psychomotor retardation, cafe au lait skin stains {73}  
  14-
U-19
male/
n.a.
PBL/ EBV line n.a.  47,XY,+mar[27]/
46,XY[3]
mar(14)(pterq23.33) array-CGH n.a. {65; 73}  
  14-
U-20
female/
12y
PBL n.a.  47,XX,+mar[100%] min(14)(pterq11.1:) acrocenM, subcenM dwarphism; potentially mat UPD 14, test not wanted by parents {0} provided by Dr. Mkrtchyan, Yerevan , Armenia  
  14-
U-21
female/
newborn
PBL de novo 47,XX,+mar[8]/
46,XX[18]
r(14)(::p11.2q12::)*
aCGH: break in q12: 30.94MB
maternal UPD 14; sSMC derived from paternal chromosome 14
SKY, array-CGH West syndrome {66}  
  14-
U-22
female/
2y
PBL n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) acro cenM, subcenM clinically abnromal {0} provided by Dr. M. Mulhatino, Rio de Janeiro, Brazil  
  14-
U-23
male/
prenatal
AF mat 47,XY,+mar[100%] der(14)t(3;14)(p24.1;q21.1) array-CGH detected prenatally, TOP {67} case 38; 73
 
 
  14-
U-24
male/
3y
PBL de novo 47,XY,+mar[10%]/
46,XY[90%]
min(14)(pterq11.2:) acro cenM, subcenM short stature, microcephaly, hypoplastic alae nasi, midface hypoplasia, cleft and lip palate, clubfeet {0} provided by Dr. Reinaldo Luna, Brasil  
  14-
U-25
male/
14y
PBL n.a. 47,XY,+mar[17]/
46,XY[3]
inv dup(14)(q11.1) acro cenM, subcenM  see below {0} provided by Dr. Iourov, Moscow, Russia
 
 
short stature, developmental delay, primary hypogonadism, congenital malformation of pancreas, secondary cardiomyopathy, bilateral myopia, retinal microangiopathy (bilateral), exophtalmos, facial dysmorphisms, abnormal dental development, prognathia, testicular hypoplasia.
  14-
U-26
female/
postnatal
PBL de novo 47,XX,+mar[11]/
46,XX[19]
min(14)t(14;19)(14pter14q11.1:
:19p13.12
19p13.2)
acro cenM, subcenM DD, short stature {68} case 7; {73}
 
 
  14-
U-27
male/
3y
PBL n.a. 47,XY,+mar[100%] der(14)t(8;14)(p23;q22) diff. FISH probe sets DD, microsomia, brachycephaly, dysmorphisms {73; 76}
 
  14-
U-28
female/
newborn
PBL mat
(balanced in mother)
47,XY,+der(14)t(8;14)(p11.1;q11.1)[100%] n.a. none Dysmorphism, hypotonia {69}  
  14-
U-29
female/
?postnatal
?PBL n.a. 47,XX,+mar[19]/
46,XX[9]
min(14)(pterq11.1:) acrocenM, subcenM n.a. {0} provided by Dr. Alves, Portugal  
  14-
U-30
female/
prenatal
AF de novo 47,XX,+mar[100%] inv dup(14)(q11.1) acrocenM, subcenM minor sonographic signs {0} provided by Dr. Borochowitz, Israel  
  14-
U-31
female/
prenatal
PBL n.a. 47,XX,+mar[100%] inv dup(14)(q11.1) acrocenM, subcenM n.a. {0} provided by Dr. Melaragno, Sao Paolo, Brasil
 
 
  14-
U-32
 
female/
6y
PBL de novo 47,XX,+mar[100%]
sSMC derivative of maternal chromosome 14
inv dup(14)(q13.2)
size 14.6 MB
array-CGH see below {62}  
multiple malformations including bilateral cleft lip and palate, coloboma, craniosynostosis, severe mental retardation, seizures and gastrointestinal dysfunction. Also mitochondrial defect with reduced function of complex I and III of the respiratory chain.
  14-
U-33
female/
postnatal
PBL mat
(balanced in mother)
47,XY,+mar[100%] der(14)t(6;14)(p25;q11.1~11.2) pericentric BAC-probe set Dysmorphism at birth {73} cases 10 and 11
 
                     

 

 

 


References

Cases with neocentromeres (N)

 

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  14-N-
qt32.1/
1-1
female/
1w
PBL de novo 47,XX,del(14)(q32.1qter), +mar[100%] inv dup(14)(qterq32.1:
q32.1
qter)*
wcp 14 see below {21-24; 27; 43}  
at birth (40 weeks of gestation): length 46.5cm; weight 2700g, OFC 34cm; facial deformities, hypertelorism, epicanthus, antimongoloid slant, deformed ears, broad base of nose, curly blond hair; marked hypertonia and jittering; subarachnoid hemorrhage over cerebral convexity; severe sleeping disorder developed during 1. year; delayed psychomotor development; at 5y normal muscle tone but marked mental deficit esp. in speech and concentration ability.
                     

 

 

N-Cases with similar imbalances NOT caused by sSMC (N-IMB)

 

                   
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result and FISH result incl. grade of mosaicism test
methods
clinical symptoms reference  
  14-N-
IMB-
q23/
1-1
1 case der(17)t(14;17)
see also {55}
{44}