tl_files/tiny_templates/Bilder TL/Header-sSMC.jpg

- sSMC -

CHROMOSOME 11

References

 

             
  Cases without
clinical findings
7 Cases with
clinical findings
10 symptoms  
  similar imbalances - no clinical findings similar imbalances with clinical findings  
  Cases with
unclear clinical correlation
Cases with
neocentromeres
2 tumor
0
 
  similar imbalances  
      DISCLAIMER      

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
mat
UPD 11
pat
UPD 11
unclear
 
           

 


the probably non-dosage sensitive pericentric region of chromosome 11


SCHEMATIC CYTOGENETIC DEPICTION

tl_files/tiny_templates/Bilder TL/sSMC/sSMC-11.jpg



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

 


Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

11p - proximal 11q - 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)(::p11.12q12.2::)
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 {42} case 11-1
 
  11-O-
p11.1/
1-1
male/
prenatal
AF de novo 47,XY,+mar[50%]/
46,XY[50%]
min(11)(:p11.1q11:) 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)(:p11.1q11:) 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)(::p11.1q12.2::)[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 DD, 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 (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?1q1?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 months
                     

 


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)(:p11.2q11:) 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)(:p11.2q11.1:) 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)(:p12q11:)
array: 40.19-54.70 MB
cenM; subcenM
array-CGH
see below {36} case Sm-5
 
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)(::p11.12q12.1::)*
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)(::p11.12q13.1::)[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/
3-2
male/
postnatal
PBL de novo 47,XY,+mar[86]/
46,XY[14]
r(11)(::p11.12q13.1::)
~1.5
MB in p and ~10.04 MB in q in euchromatin
pericentric BAC-set see below {39} case 5  
  twin pregnancy - other twin normal; at birth all values at 3rd centile; at 15 months normal growth parameters; but opsychomotor retardation and dysmorph  
  11-W-
p11.12/
4-1
male/
prenatal
AF de novo 47,XY,+mar[100%] min(11)(:p11.2q11:
: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}  
  11-W-
IMB-
q11/
2-1
male/
postnatal
PBL de novo 46,XY,dup(11)(q12.1q13.3)[53%]/46,XY[47%] aCGH dysmorphic features {40} case 3
 
                   


W-cases with unclear/insufficient characterization of the sSMC (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  
  11-
CW-4
female/
4y
PBL de novo 47,XY,+mar[70%]/46,XY[30%] mar(11) - size 5.9 Mb array-CGH intellectually disbaility, mild dysmporphism, macrocephaly {34}  
                     

 

 


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)(::p11.2q13.1:
: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)(::p11q12::) 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)(::p11q12::)[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)(:p11.1q11:) cenM; subcenM n.a. {0} provided by J. Melo, Coimbra, Portugal  
  11-
U-9
female/
5m
PBL mat 47,XX,+mar[30] r(11)(::p11.1q12.2::)[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)(:p11.1q11:) 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)(:p12q11:)
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)(::11p11.111q12.1:
: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; 38}  
  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; 38}  
  11-
U-15
female/
prenatal
AF de novo 47,XX,+mar[60-90%]/
46,XX[10-40%]
min(11)(:p11.21q13.1:)
hg 19: 49.85-64.60Mb
aCGH hg18: 48,191,873-?59,180,308 Mb
cenM; subcenM;
aCGH
see below {35} case 12  
  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  
  11-
U-16
male/
prenatal
AF de novo 47,XY,+mar[15]/
46,XY[17]
min(11)(:p11.?1q1?1:) cenM; subcenM Advanced maternal age, no other info available {0} case provided by Dr. Alves, Porto, Portugal
 
  11-
U-17
female/
prenatal
AF n.a. 47,XX,+mar[94]/
46,XX[53]
min(11)(:p11.11q12.3:)
aCGH: 55.51-62,11
aCGH Advanced maternal age, TOP no other info available {37} case 13  
  11-
U-18
female/
prenatal
AF de novo 47,XX,+mar[33]/
46,XX[25]
min(11)(:p13q12.1:)
aCGH: 34.89-56,41
aCGH AMA, n.a. {41} case AF-11  
  11-
U-19
female/
prenatal
AF de novo 47,XX,+mar[71]/
46,XX[22]
min(11)(:p11.1q12.1:)[3]/
r(11)(::p11.2
q12.1::)[2]/
r(11;11)(::p11.2
q12.1:
:p11.2
q12.1::)[3]
cenM; subcenM AMA, enhanced nuchal translusiency {0} provided by Bioarktis, Greece  
  11-
U-20
male/
prenatal
AF n.a. 47,XY,+mar[2]
/46,XY[48]
min(11)(:p11.11q11:)  cenM; subcenM AMA {0} provided by Dr. Alves, Portugal  
  11-
U-21
male/
prenatal
AF n.a. 47,XY,+mar[20%]/
46,XY[80%]
mar(11)(:p14.1q12.1:)
arr[hg19] 30,80-56,65 Mb
cep;
aCGH
TOP; n.a. {0} perovided by Dr. Manolakis, Greece  
                     

 


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)(qterq22::q22qter) 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}