FISH

SMALL SUPERNUMERARY MARKER CHROMOSOMES

- sSMC 11 -

           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 11   maternal   paternal   unclear

the probably non-dosage sensitive pericentric region of chromosome 11

 

SCHEMATIC CYTOGENETIC DEPICTION                    
  sSMC-11DISCLAIMER

 

 

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]

 critical region 50.47 --- 50.95 uncritical region   [51.40 centromere 56.40]   uncritical region 60.23 --- 65.02 critical region

Below adapted for UCSC hg19, 2009

 critical region 50.47 --- 50.95 uncritical region   [51.60 centromere 55.70]   uncritical region 60.43 --- 65.22 critical region

 DISCLAIMER

 

 Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

11p - proximal

 1q - proximal

symptoms

brain malformations

 (100%) -

developmental delay

 (100%) -

dysmorphic face

 (100%) -

hypotonia

 (100%) -
number of cases (marked with “°” below) 1 0


 

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  
  11-O-
p15.1/
1-1		 see McCl-11-O-p15.1/1-1   {26}  
  ***
11-O-
p11.2/
1-1
 ***		 male/
40y		 PBL n.a. 47,XY,+mar[100%] r(11)(::p11.12→q12.2::)
 SNP-data: 50,952,568-60,230,397		 array-CGH;
humanCytoSNP-12v2; Illumina Karyostudio v1.2; UPD-test		 IVF patient; hypoplasia testes bilat., FSH elevation {0} provided by Dr. Jiří Horáček, Praha, Czech Rep.  
  11-O-
p11.1/
1-1		 male/
prenatal		 AF de novo 47,XY,+mar[50%]/
46,XY[50%]		 min(11)(:p11.1→q11:) cenM; subcenM; UPD-test amniocentesis due to advanced maternal age; ultrasound of fetus was normal Normal child was born. Child normal at 1 month. {0}provided by Dr. Sagi (Israel)  
  11-O-
p11.1/
1-2		 male/
prenatal		 AF de novo 47,XY,+mar[21]/
46,XY[32]		 min(11)(:p11.1→q11:) cenM; subcenM amniocentesis due to advanced maternal age; Normal child was born. Child normal at 3 month. {0}provided by Dr. Junge, Dresden, Germany  
  11-O-
p11.1/
2-1		 female/
24y		 PBL n.a. 47,XX,+mar[100%] r(11)(::p11.1→q12.2::)[10]/
r(11)(::p11.1→q12.2:
:q12.2→p11.1::)[7]/
min(:q12.2→p11.1:
:p11.1→q12.2:)[3]
FISH-data:  RP11-77M17 (57.28) on sSMC		 cenM; subcenM; UPD-test normal female; sSMC detected due to developmental delay, muscular hypotonia, macrocephaly in 5m old daughter; {0} provided by Dr. Belitz, Berlin, Germany  
                     

 

O-Cases with similar imbalances NOT caused by sSMC (O-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  
  11-O-
IMB-
p11.2/
1-1		 female/
prenatal		 AF; PBL de novo 46,XX,dup(11)(p11.2q11.1) subcenM normal child at 2 years {25}  
  11-O-
IMB-
p11.2/
2-1		 female/
15y		 PBL de novo 46,XX,dup(11)(p11.2p11.1)
BAC-FISH  duplication size ~6MB		 wcp 11, BACs normal child apart from isolated learning disability, particularly dyscalculia. {27}  
  11-
O-IMB
p11.11/
1-1		 female/
39y		 PBL n.a. 46,XX,dup(11)(p11.1q11) cep probe 11 normal pregnant women - also in unborn child and later born normal child {24}  
                   

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  
  11-
CO-
1		 female/
34y		 PBL paternal
father with sSMC in 59% of PBL and 31% of fibroblasts		 47,XX,+mar[60%]/
46,XX[40%]		 r(11) centromeric probes including cep11; telomeric probes; electron microscopy see below {7}  

34y old normal woman, sSMC detected due to presence of sSMC in father who suffered from progressive systemic sclerosis  and complete CREST syndrome, starting at 59y of age
  11-
CO-
2		 male/
prenatal		 AF de novo 47,XY,+mar[32]/
46,XY[12]		 r(11)(::p1?1→q1?1::)* different centromeric probes, wcp 11, 2 centromere near (?) BACs see below {15} case 29
{16} case 26		  

amniocentesis due to advanced maternal age. normal child born, normal at 3 moths
                     

 

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  
  11-W-
p11.2/
1-1		 female/
postnatal?		 PBL? n.a. 47,XX,+mar[53%]/
46,XX[47%]		 mar(11)(:p11.2→q11:) array-CGH abnormal {31} case 29361  
  11-W-
p11.2/
1-2		 male/
prenatal		 fetal tissue n.a. 47,XY,+mar[77%]/
46,XY[23%]		 mar(11)(:p11.2→q11.1:) cenM; subcenM
 		 missed abortion in 7+1 week of gestation {0} provided by Dr. Altus, Magdeburg, Germany  
  ***
11-W-
p11.12/
1-1  °
 ***		 male/
3y		 PBL de novo 47,XY,+mar [33%]/46,XY[67%] min(11)(:p12→q11:)
array: 40.19-54.70 MB		 cenM; subcenM
array-CGH		 see below {0} provided by Dr. Leipoldt, Freiburg, Germany  

Child born after normal pregnancy. At birth normal values and no signs of dysmorphism, however, psychomotor developmental delay. Walking with 20m, speech from age of 5y; at 18y speech almost normal. Muscular hypotonia. Face different from that of one brother and one sister. Dandy Walker brain abnormality acc. to MRT.
  11-W-
p11.12/
2-1		 n.a/
postnatal		 PBL de novo 47,+mar [14%]/
46[86%]		 r(11)(::p11.12→q12.1::)*
size in p-arm 0.2 MB and in q-arm 2.3 MB		 n.a.; subcenM with 3 BACs see below {19} case 13  

Hypotonia; gross motor delay; seizures; macrocephaly; intermittent exotropia.
  ***
11-W-
p11.12/
3-1
 ***		 female/
13y		 PBL mat 47,XX,+mar[70%]/
46,XX[30%]		 r(11)(::p11.12→q13.1::)[6]/
r(11;11)(::p11.12→q13.1:
:p11.12→q13.1::)[3]/
min(11)(:p11.12→q13.1:)[4]
 Array: 50.47-65.02 MB		 midi subcenM
array-CGH; UPD-test		 see below {0} provided by Joana Melo , Coimbra, Portugal  

at 13 years: Facial dysmorphism, strabismus, ptosis, discrete mental retardation and developmental delay. However, mother with 36 years: No apparent mental retardation. Only congenital cardiopathy (corrected with surgery) reported.
  11-W-
p11.12/
4-1		 male/
prenatal		 AF de novo 47,XY,+mar[100%] min(11)(:p11.2→q11:
:q11→p11.2:)		 cenM; subcenM; UPD-test see below {0} provided by Dr. Lemmens, Aachen, Germany  

advanced maternal age; child spontaneously aborted 22 week of gestation
                     

 

 

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  
  11-W-
IMB-
p12/
1-1		  male/
53y		 PBL n.a. 46,XY,dup(11)(p12) n.a. mild to moderate mental retardation, short stature, discrete minor anomalies. {29}  
  11-W-
IMB-
p11.2/
1-1		  male/
5m		 PBL maternal
(balanced)		 46,XY,ins(11)(11;11)(q14.5p14.1p11.2) n.a. macular dysfunction, cleft lip and palate, and developmental delay {22}  
  11-W-
IMB-
q11/
1-1		  male/
5m		 PBL n.a. 46,XY,dup(11)(q11q13.3)[29]/46,XY[6] Locus specific probes multiple craniosynostoses, congenital heart defect and developmental delay {23}  
                   

 

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  
  11-
CW-1		 female/
4y		 PBL de novo 47,XX,+mar[?]/
46,XX[?]		 min(11) FISH probe (D11Z1) see below {4} case 7  

born by cesarean section in gestational week 30; weight: 1250g; length 40cm; head circ.: 27,5cm - i.e. normal for gest. age; micrognathia; low-set ears; motor and mental development retarded. At age of 4.8y body measurements at 3rd percentile; minor hypertelorism; epicanthus; broad nasal bridge; long philtrum, carious teeth
  11-
CW-2		 male/
1. prenatal
2. at birth
3. 9m

1. AF; 
2. PBL
3. Fibroblasts

 n.a. 1. 47,XY,+mar[52%]/46,XY[48%]
 2. 46,XY [200]
3. 47,XY,+mar[36%]/46,XY[64%]		 r(11) telomeric; all centromeric probes  in an array;  see below {5} case 7  

developmental delay and moderately retarded at age of 4y; at birth:  cleft soft palate, VSD, wet lung; hypertonia and short statures at age of 7m; minor dysmorphic features
  11-
CW-3		 male/
child


PBL

 de novo 48,XY,+mar1,+mar2[?]/
47,XY,+mar1[?]/
47,XY,+mar2[?]/
46,XY[?]		 mar 1: mar(11)
mar2: ?		 different cep-probes mild psychomotor delay {14} case 4  
                     

 

 

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  
  11-
U-1		 male/
47y		 bone marrow de novo
acquired		 47,XY,+mar[18]/
46,XY[2]		 r(11)(::p11.2→q13.1:
:q14::)
array-CGH: 42.07-60.60 MB
 r(11)(::p11.2→q12.3::q14::)		 midi;
MCB;
cenM;
CGH; array-CGH		 Atypical chronic myelogeneous leukemia (CML); sSMC only in bone marrow, not in peripheral blood  {0}
{1} case 16
{2} 
{3} case 14		  
  11-
U-2		 see mult 2-10   {6}  
  11-
U-3		 male/
prenatal		 AF de novo 47,XY,+mar[31]/
46,XY[5]		 r(11)(::p11→q12::) n.a. Amniocentesis due to advanced maternal age, no ultrasound abnormalities; TOP {12} case 4  
  11-
U-4		 see mult 2-27   {17} case 6  
  11-
U-5		 n.a./
n.a.		 n.a. n.a. 47,+mar[?%] mar(11) centromeric probes no info available {18}1 case  
  11-
U-6		 see mult 2-28   {0} provided by J. Anderson, Brisbane, Australia  
  11-
U-7		 n.a./
prenatal		 AF n.a. 47,+mar(11)[50%]/
46[50%]		 r(11)(::p11→q12::)[3]/
r(11;11)(::p11→q12:
:p11→q12::)[2]		 cenM; subcenM n.a. {0} provided by J. Melo, Coimbra, Portugal  
  11-
U-8		 n.a./
prenatal		 AF n.a. 47,+mar(11)[70%]/
46[30%]		 min(11)(:p11.1→q11:) cenM; subcenM n.a. {0} provided by J. Melo, Coimbra, Portugal  
  11-
U-9		 female/
5m		 PBL mat 47,XX,+mar[30] r(11)(::p11.1→q12.2::)[10]/
r(11)(::p11.1→q12.2:
:q12.2→p11.1::)[7]/
min(:q12.2→p11.1:
:p11.1→q12.2:)[3]		 cenM; subcenM; UPD-test developmental delay, muscular hypotonia, macrocephaly, mother normal {0} provided by Dr. Belitz, Berlin, Germany  
  11-
U-10		 female/
6y		 PBL n.a. 47,XX,+mar[100%] min(11)(:p11.1→q11:) cep probes subcenM developmental delay {0} case provided by Dr. Kozlowski, Düsseldorf Germany  
  11-
U-11		 female/
prenatal		 AF de novo 47,XX,+mar[21]/
46,XX[30]		 mar(11)(:p12→q11:)
distal break at 43.085MB		 array-CGH n.a. {0} case provided by Dr. Joleen Viront, Akron, OH, USA  
  11-
U-12		 female/
prenatal		 AF de novo 47,XX,+mar[13]/
46,XX[10]		 r(11)t(11;20)(::11p11.1→11q12.1:
:20q13.1?2→q13.32::)		 midi, subcenM; UPD-test advanced maternal age, no US-abnormalities, pregnancy continued - patient lost during follow-up {0} case provided by Dr. Schwaab, Wiesbaden, Germany  
  11-
U-13		 male/
postnatal		 PBL pat
(balanced t(11;13)(q25;q14))		 47,XY,t(11;13)(q25;q14),+mar der(11)t(11;13)(q25;q14) n.a. mental retardation and developmental delay. dysmorphic signs {32}   
  11-
U-14		 male/
prenatal		 AF de novo 47,XY,+mar[10]/
46,XY[5]		 mar(11) array-CGH, FISH IUGR; spontaneous abortion in week 20 {33}   
  11-
U-15		 female/
prenatal		 AF de novo 47,XX,+mar[60-90%]/
46,XX[10-40%]		 min(11)(:p11.21→q13.1:)
hg 39: 49.85-64.60Mb		 cenM; subcenM;
aCGH		 advanced maternal age, normal sonography; at birth weight: 25th centile, lenght  < 3. centile, OFC 40. centile. VSD; later on good gain of weight and deleyed development with muscular hypotpnia; large occiput, minor dysmorphic signs
 {0} case provided by Dr. Dufke, Tübingen, Germany  
                     

 

 

 

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  
  11-N-
qt22/
1-1		 male/
1w		 PBL/
fibroblasts		 de novo 47,XY,del(11)(q22),+mar[100%]
(sSMC in fibroblasts 100%)		 inv dup(11)(qter→q22::q22→qter) alpha-, beta-satellite satIII probes, telomeric, all wcp, YAC-probes (not specified) mental retardation and/or developmental delay or structural anomalies detected at birth {8} case 6
{9; 10; 13; 20}		  
  11-N-
p11.2/
1-1		 see McCl-11-N-p11.2/1-1 {20; 21}  
                     

 

 

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  
  11-
N-IMB-
p15/
cases		 see {28} {28}  
  11-N-
IMB-
q22/
cases		 see {30} {30}