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

- sSMC -

CHROMOSOME 3

References

 

             
  Cases without
clinical findings
21 Cases with
clinical findings
10 symptoms  
  similar imbalances - no clinical findings similar imbalances with clinical findings  
  Cases with
unclear clinical correlation
Cases with
neocentromeres
11 tumor
4
 
  similar imbalances  
      DISCLAIMER      

IIn 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 3
mat
UPD 3
pat
UPD 3
unclear
 
           

 


the probably non-dosage sensitive pericentric region of chromosome 3


SCHEMATIC CYTOGENETIC DEPICTION

tl_files/tiny_templates/Bilder TL/sSMC/sSMC-3.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 ? --- 74.67 uncritical region [89.40 centromere 93.20] uncritical region 104.78 --- ? critical region

Below adapted for UCSC hg19, 2009

critical region ? --- 73.17 uncritical region [87.90 centromere 93.90] uncritical region 105.48 --- ? critical region

 


Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

3p - proximal 3q - proximal
symptoms
growth retardation (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  
  03-O-
p12.2/
1-1
male/
45y
PBL n.a. 47,XY,+mar[15] min(3)(:p12.2q11.1:)
FISH-data: RP11-91A15 (89.6 MB) on sSMC
cenM
subcenM
ICSI-patient; no clinical signs at age of 45 {1} case 8
{2} case 2
{37} case 6
{56} case 3-1
 
 
03-O-

p12.1/
1-1
male/
51y
PBL n.a. 47,XY,+mar[6]/
46,XY[14]
min(3)(:p12.1
q11.1~11.2:)[55]/
min(3)(:p11.1

q11.1~11.2:
:q11.1~11.2

p11.1:)[2]
FISH-data: RP11-91A15 (89.6 MB) RP11-21I16 (96.01 MB - hg2006; 94.53 MB - hg2009) on sSMC
midi Normal male with fertility problems and depression; cryptorchidism, small testes, umb. and ing. hernia. {37} case 7
{56} case 3-2
 
  03-O-
p12.1/
2-1
female/
prenatal
AF n.a. 47,XX,+mar[16]/
46,XX[33]
dic(3)(:p12.1q11.2:
:q11.2
p12.1:)[12]/
min(3)(:p12.1
q11.2:)[3]/
r(3)(::p12.1
q11.2::)[1]
FISH-data: RP11-91A15 (89.6 MB) and RP11-21I16 (96.01 MB - hg2006; 94.53 MB - hg2009) on sSMC
cenM
subcenM
aCGH
see below {56} case 3-3
 
Amniocentesis CVS in week 14+4 due to advanced risk in 1. trimenon screening (1:280), normal child born with APGAR 9/9/10; weight 3650g, length 50cm; at 8 years developmental retardation, microcephaly, seizures, no language
 
03-O-

p12.1/
3-1
n.a./
prenatal
AF n.a. 47,XN,+mar[?%] min(3)(:p12.1
q12.2:)
array
-data: size 12.7 Mb
aCGH advanced maternal age, normal child born {54} case 4
{56} case 3-4
 
  03-O-
p12.1/
2-2
female/
29y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[17%]/
46,XX[83%]
r(3)(::p12.1q11.1::)[14]/ min(3)(:p12.1q11.1:)[5]/ min(3)(:p12.1q11.1:
:q11.1
p12.1:)[2]
FISH-data: RP11-91A15 (89.6 MB) on sSMC;
aCGH: 89,269,203-90,149,349
midi
subcenM
aCGH
Normal female {0} provided by Dr. G. Krüger, Rostock. Germany  
  03-O-
p12.1/
3-1
female/
37y
PBL n.a. 47,XX,+mar[17]/
46,XX[33]

mar(3)(:p12.1q11.1:)
aCGH hg19: 83,610,388-90,192,224
aCGH hg18;
83,810,388-89,400,000

aCGH infertility (in vitro failures) {0} provided by Dr. A. Jezela-Stanek, Instytut-Pomnik "Centrum Zdrowia Dziecka, Warsaw, Poland  
  03-O-
p12.1/
3-2
male/
50y
PBL n.a. 47,XY,+mar[8]/
46,XY[2]
mr(3)(::p12.1q11.1::)[6]/
min(3)(:p12.1q11.1:)[2]
cenM
subcenM
normal male, repeated abortions in partnership {0} provided by Dr. B. Belitz, Berlin, Germany  
  03-O-
p12/
1-1
male/
prenatal
AF de novo 47,XY,+mar[100%] min(3)(:p12q10:) midi see below {8} case 1  
Amniocentesis due to advanced maternal age. A healthy boy was delivered at term. At 20m of age the development of the child was still normal.
  ***
03-O-

p11.2/
1-1
***
female/
37y
PBL de novo 47,XX,+mar[100%] min(3)(:p11.2q11.1:)

aCGH: 74.67-104.78
FISH-d
ata: RP11-312H1 (87.6 MB) on sSMC

array-CGH (Agilent 44000); FISH Normal female with one 15 years old daughter. One miscarriage at 5 months of gestation {0} provided by Dr. F. Sheth, Ahmedabad, India  
  ***
03-O-
p11.2/
2-1
***
female/
35y
PBL n.a. 47,XX,+mar[5]/
46,XX[10]
r(3)(:p11.2q12.1:)

aCGH: 3p12.3q13.11 77,503,851-105,005,564 Mb
FISH-confirmed

cep probes, subcenM; MCB; array-CGH Physically normal female; in childhood repeated infections, developmentally retarded and language development problems {51} case 1
{52} case Sr-3
 
  03-O-
p11.1/
1-1
male/
newborn
PBL de novo 47,XY,+mar[100%] min(3)(:p11.1q11.1:) cenM, subcenM studied postnatal cytogenetically due to free trisomy 3 in chorion {0} provided by Dr. O.A. Haas, Vienna, Austria  
  03-O-
p11.1/
1-2
male/
prenatal
AF de novo 47,XY,+mar[25]/
46,XY[19]
min(3)(:p11.1q11.1:) cenM, subcenM Amniocentesis due to M. Hodgkin and chemotherapy 10 years ago; normal child born and normal at 2 years of age {0} provided by Dr. Mehnert, Neu-Ulm, Germany  
  03-O-
p11.1/
1-3
male/
prenatal
CH n.a. 47,XY,+mar[22]/
46,XY[189]
min(3)(:p11.1q11.1:) cenM, subcenM in sonography one lacking kidney; apart from that normal child born {0} provided by Dr. Junge, Dresden, Germany
 
  03-O-
p11.1/
1-4
male/
adult
PBL n.a. 47,XY,+mar[84%]/
46,XY[16%]
min(3)(:p11.1q11.1:) cenM, subcenM normal male, infertile {0} provided by Dr.Emmanulakis, Athens, Greece
 
  03-O-
p11.1/
2-1
female/
adult
PBL de novo 47,XX,+mar[100%] min(3)(:p11.1q11.2:) pAEO.68; RP11-631O4 Studied due to one second trimester miscarriage {46} case P-1, {55}
 
  03-O-
p11.1/
3-1
male/
33y
PBL n.a. 47,XY,+mar[15%]/
46,XY[85%]
min(3)(:p11.1q12:) cenM, subcenM Studied due to fertilty problems {0} provided by Dr. Iuorov, Moscow, Russia  
  ***
03-O-

p10/
1-1
***
male/
prenatal
AF maternal
[33%]
47,XY,+mar[41%]/
46,XY[59%]
r(3)(::p10q13.1::)
FISH-data: RP11-21I16 (96.01 MB - hg2006; 94.53 MB - hg2009) on sSMC
midi Advanced maternal age. Mother normal; at nine months of age the development of the child was still normal.
{5} cases E; F  
  ***
03-O-
p10/
2-1
***
n.a./
prenatal
CH maternal
[5-6%]
47,+mar[56%]/
46[44%]
r(3)(::p10q12::)
FISH-data: RP11-21I16 (96.01 MB - hg2006; 94.53 MB - hg2009) on sSMC
midi;
UPD-test
Normal at autopsy; mother normal {5} cases B; C  
                     

 

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

none reported yet


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  
  03-
CO-1
male/
prenatal
AF de novo 47,XX,+mar[80%]/
46,XX[20%]
min(3) FISH probe (D3Z1) see below {3} case 6  
Amniocentesis due to advanced maternal age and 3 previous abortions; pregnancy terminated; pathology of the fetus was normal at 18 weeks of gestation.
  03-
CO-2
female/
7m
PBL de novo 47,XX,+mar[56%]/
46,XX[44%]
min(3) .ish D3Z1+, wcp3+ different FISH probes normal apart from a dysplastic kidney {3} case 5  
  03-
CO-3
female/
30y
PBL de novo? 47,XX,+mar[20]/
46,XX[80]
r(3) SKY; wcp3 repeated abortions {19} case 5
{37} case 8
{56} case 3-5
 
  03-
CO-4
n.a./
prenatal
AF de novo 47,+mar[?%] r(3) n.a. normal sonography {44} 1 case  
                     

 


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  
  03-W-
p12.3/
1-1
male/
5y
PBL de novo 47,XY,+r[11]/
46,XY[9]
r(3)(::p12.3q11.2::)
aCGH: 81.47-99.78 MB
different FISH-probes; aCGH see below {49} case 5  
global developmental delay, sagittal craniosynostosis, intermittent right eye extropia, small nares, small cupped-shaped ears, patent ductus arteriosus, scoliosis, small phallus and clinodactyly
  03-W-
p12.1/
1-1
female/
prenatal
AF de novo 47,XX,+mar[100%] min(3)(:p12.1q11.2:)
FISH-data: RP11-21I16 (96.01 MB) on sSMC
cenM; MCB, subcenM see below {20}  
Amniocentesis due to abnormal results in ultrasound scan in week 20; growth retardation of three weeks, oligohydramnion and dolichocephalos. In week 21 the fetus was spontaneously aborted. An autopsy was not performed.
  03-W-
p12.1/
2-1
female/
8y
PBL
cell line at ECACC DD0767
de novo 47,XX,+r[4]/
46,XX[46]
r(3)(::p12q13.2::)[12%]/
r(3)(::p12
q13.2::p12q13.2::)[12%]
FISH-data: RP11-21I16 (96.01 MB) on sSMC
all centromeric probes; wcp 3;
cenM; subcenM; MCB;
UPD-test
see below {4} case 2
{12} case 2
{27} case 1
 
Mild developmental delay, short stature; suspicion of Turner syndrome; slow language
  03-W-
p11/
1-1
see McCl-03-W-p11/1-1
{16; 32}{33}case 1  
  03-W-
p10/
1-1
female/
1y
PBL de novo 47,XX,+r[70%]/
46,XX[30%]
r(3)(::p10q11::) midi see below {9} case 1  
child born with slight dysplastic features; muscular hypotonia and feeding difficulties in neonatal period; normal psychomotor development
                     

 

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  
  03-W-IMB-q11.1/
1-1
male/
20m
PBL maternal
(intrachromosomal insertion in 3p26.2)
46,XY,ins(3;3)(p26.2;p11.1p14.2) n.a. developmental delay, hypertelorism, facial dysmorphism, ptosis, simian crease,clinodactyly, hypotonia, growth retardation
{41}  
                   

 

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  
  03-CW-1 female/
2.5m
PBL maternal
(in 3% of  PBL)
48,XX,+2mar[50]/
47,XX,+r[36]/
46,XX[14]
mar(3) .ish (wcp+, D3Z1+) wcp3; cep3 see below {10}  
Uncomplicated pregnancy and delivery, APGAR 3/7; feeding difficulties, lethargy and arrest in linear growth at 10w of age. Dysmorphic signs with small nose, a tented upper lip and relative macrocrania; frontal bossing, anteverted nares; hypotonic with poor visual tracking; cerebellar astrocytoma was detected and removed, followed by 1y chemotherapy; delay in speech development; growth development continues along less than the 5th percentile.
  03-CW-2 n.a./
prenatal
AF de novo 47,+mar[?%] r(3) n.a. abnormal sonography; TOP {44} 1 case  
  03-CW-3 female/
7y
PBL de novo 47,XX,+mar[17]/
46,XX[3]
mar(3)(p?q?) wcp 3 see below {47}  
high triangular forehead, hypertrichosis, wide spaced eyes, ptosis, down-slanting palpebral fissures, strabismus, broad nasal root, very short nose with anteverted nares, short grooved philtrum, triangular mouth, high narrow palate, micrognathia, malformed ears with preauricular sinus on one of sides and skin lesions, corpus callosum agenesis and hydrocephaly, abnormal feet position.
  03-CW-4 male/
2y
PBL n.a. 47,XY,+mar[?%]/
46,XY[?%]
min(3) SKY DD {50} case F0613262  
  03-CW-5 male/
2y
PBL n.a. 47,XY,+mar[100%] min(3) SKY delayed milestones {50} case F0732043  
                     

 

 


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  
  03-
U-1
see mult 2-1
{6} case 2  
  03-
U-2
see mult 2-2 {7}  
  03-
U-3
see 03-CO-3    
  03-
U-4
female/
prenatal
AF de novo 47,XX,+mar[100%] r(3) SKY amniocentesis due to advanced maternal age; normal ultrasound in weeks 18 and 24 of gestation {19} case 4  
  03-
U-5
n.a./
prenatal
AF de novo 47,+mar[63%]/
46[37%]
r(3)(::p10q12::) midi see below {5} case D  
Amniocentesis due to advanced maternal age. The parents' chromosomes were normal, and they elected to terminate the pregnancy in week 18. No fetal abnormalities were found at autopsy.
  03-
U-6
see mult2-14 {11} case 28  
  03-
U-7
n.a./
n.a.
n.a. n.a. 47,+mar[?%] mar(3) wcp probes no info available {38} 1 case  
  03-
U-8 °
female/
prenatal
CH, AF de novo 47,XX,+mar[100%] min(3)(:p12.2q10:)*
+3 in short term culture; mat UPD 3
BAC probes, MLPA; UPD-test see below {42}
{45 case 1}
 
twin pregnancy; in chorion (short term culture) in twin 2 a trisomy 3 (100%) was detected; in long term culture in 100% of cells had sSMC; twin 2 significantly shorter than twin, IUGR 1; sSMC also found in amnion cells; selective fetocide was done, however, after 3 weeks death delivery of both twins.
03-
U-9
male/
prenatal
AF n.a. 47,XY,+mar[100%] min(3)(:p11.2~11.1
q11.1~11.2:)
cenM/ subcenM
n.a. {0} provided from Portugal
                     

 


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  
  03-N-1 n.a./
prenatal
AF de novo 47,+mar[17%]/
46[83%]
neo(3) cep 3, wcp 3 see below {45} case 15  
sonographic abnormalities: clubfeet, clenched hands, right hydronephrosis, ventricular dilatation, TOP; fetopathology: facial dysmorphism: dolichocephaly, microretrognathism, upslanted palpebral fissures, low-set ears, synophris Ventricular dilatation, clubfeet, clenched hands, narrow chest, nephromegaly, didelphic uterus
  03-N-
qt25.33/
1-1
female/
1m
PBL; fibroblasts de novo PBL: 46,XX
fibro: 47,XX,+inv dup(3)(qter→q25.33::q25.33→qter)[100%]
subtel 3qter; array-CGH see below {39}  
dysmorphic features;  pregnancy and delivery at term were normal. Birth weight was 2200g, length 45cm and head circumference 32cm. At birth: prominent hairy forehead with hair extending up to the cheeks, upslanting palpebral fissures, depressed nasal bridge with short nose and very smooth philtrum, thin upper lip which was turning downward, low set ears, micrognathia , chubby cheeks, contracture of the fingers with postaxial polydactyly of left hand, widely separated toes which were overlapping, streaky pigmentation on the inner aspect of both fore arms distributed along the lines of Blaschko. Ophthalmological exam was normal. Echocardiography showed sub-aortic ventricular septal defect (VSD), pulmonary hypertension and moderate valvular pulmonary stenosis. Skeletal survey showed a tiny projection of the tip of coccyx, a tail-like sacrococcygeal appendage. Computed tomography scan of  the lumbosacral spine showed prominence of coccyx and outward projection. Magnetic resonance imaging of the brain showed partial hypoplasia of the corpus callosum and slight hypoplasia of the cerebellum.
  03-N-
qt26/
1-1
male/
50y
abdominal wall metastasis of a lung sarcanoid carcinoma de novo; acquired GTG and FISH result combined:
67~71
<3n>,XX,der(Y)t(Y;14)(p11;q11),del(1)(q23),1der(?1)t(3;15;1;14)
(3?q;15q?;1?q;14q?),der(2)t(2;20)(p23;?),der(2)t(2;17)(q13;q11?),del(3)
(q21),del(3)(q21),
+i(3)(qter→q26::q26→qter)x2,del(6)(?q21),+der(6)t(6;17)
(?;?),del(7)(q21),
+der(8)t(8;21)(?;q21),der(9)t(9;3;13)(q12;?;q11),der(9)
t(6;9)(q15?;q21),
+i(9)(pter→p23::p23→pter)x4~6,10,der(11)i?(11)(q10?),
-13,der(14)t(14;15)(?;?),der(14)t(14;3;?)(?;?;?),15,der(13;15)(q10;q10),
-16,der(17)t(9;17)(p11;q11),-18,19,der(19)t(2;19)(?;q?11),del(21)(q21),
-22,der(22)t(17;22)(?;q11)[cp20].
M-FISH, various probes as listed in {29}

array-CGH

see below {25}  
A 50-year-old man presented with a history of cough, hemoptysis, and thoracic pain (regular smoker); cavitating tumor of the right upper lobe diagnosed ( T2 N0 M0). right upper lobectomy showed an excavated tumor 6x5x3 cm. The tumor cells positive for cytokeratin 7, not for cytokeratin 20. Sarcomatoid carcinoma of the lung of the pleomorphic carcinoma subtype was diagnosed. One month after surgery, the patient developed a subcutaneous metastasis on the right thigh (M1). Chemotherapy with cisplatin (100 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1, 8, 15, and 22 of a 28-day cycle), but after three cycles the patient progressed with the development of multiple subcutaneous metastases. One of the abdominal wall metastases (M2) was resected for palliative intent 8 months after the initial diagnosis. After two additional lines of chemotherapy, the patient died of progressive disease 13 months after the initial diagnosis.
  03-N-
qt26/
2-1
male/
10y
bone marrow, lymph node cells; pleural fluid cells de novo
acquired
marker present one time each in 15/15 lymph node cells
in 5/14 and two times each in 5/14 pleural fluid cells
in unstimulated bone marrow trisomy 3 in 10/15 cells and 2 /15 cells with marker
inv dup(3)(qterq2?6: :q2?6qter) wcp and FISH with different probes B-cell lymphoma {26; 32}  
  03-N-
qt26/
2-2
male/
3.5y
bone marrow, lymph node cells; pleural fluid cells de novo
acquired
marker present one time each in 15/15 lymph node cells
in 10/14 in pleural fluid cells; duplicated marker in 5/10 of these cells
in unstimulated bone 47,XY,+3[10]/47,XY,+mar[2]/46,XY[3]
inv dup(3)(qterq26: :q26qter) wcp and FISH with different probes T-cell lymphoma - case maybe the same as 03-N-q26/2-1. {28}  
  03-N-
qt26.2/
1-1
male/
prenatal
skin fibroblasts
cell line at ECACC DD3329
de novo 47,XY,+mar[17]/
46,XY[13]
inv dup(3)(qterq26.2: :q26.2qter)
(sSMC derivatve of mat. chr. 3)
all cep probe, M-FISH, sub-telomeric probes 3p and 3q; UPD-test see below {14; 18; 22; 32}  
Pregnancy terminated due to abnormal ultrasound scan, necropsy demonstrated presence of high arched palate with small amount of postnuchal edema, single transverse palmar crease on right hand, on the back a 1.3cm long lumbosacral myelomengiocele, Arnold-Chiari-malformation, asymmetry of the kidneys, renal dysplasia
  03-N-
qt26.2/
1-2
male/
1d
PBL/ fibroblasts de novo 47,XY,+mar[1]/
46,XY[39]
mar in 35/40 fibroblasts
inv dup(3)(qterq26.2: :q26.2qter) pan-centromeric probe; telomeric probe; wcp3 subtel 3q see below {17} case 2; {18; 22; 32}  
Born by vaginal delivery at 36 weeks of gestation; birth weight 2,905 g (25th centile); Prenatal ultrasound had shown a megaureter and an enlarged kidney on the right side. At 4 weeks, his growth parameters were all at the 25th centile. The skin showed streaky hyperpigmentation with whorl-like and streaky patterns that were most pronounced over the trunk and extremities; wide open anterior and open posterior fontanel, ocular hypertelorism, upslanting eyes, depressed nasal bridge, and a preauricular pit on the right side. Accessory nipples were present bilaterally. Testicles were undescended. His hands showed bilateral miniature postaxial polydactyly, clinodactyly of the 5th fingers with only one flexion crease, mild flexion contractures of the metacarpophalangeal joints of other fingers, and bilateral transverse palmar creases. Rocker bottom feet and eversion of the right foot were present. At age 6 weeks, he developed tonicclonic seizures; left cerebral ventricle that was slightly bigger than the right by computed tomography scan; right pulmonary artery stenosis; duplication of the right kidney with hydronephrosis and a normal left kidney; slight nystagmus; psychomotor delayed; mild delay in all areas of development.
  03-N-
qt26.2/
1-3
male/
10y
PBL/ fibroblasts de novo 46,XY in PBL
47,XY,+mar[mos] in fibroblasts
inv dup(3)(qterq26.2: :q26.2qter) midi, sub-telomere 3q see below {21; 32}  
Suspicion of bilateral Perthes disease; mild developmental delays, attention deficit-hyperactivity, macrocephaly, asymmetries of the hands and of the legs, linear and swirly arrays of irregular skin pigmentation and areas of focal skin atrophy, both distributed in a manner consistent with lines of Blaschko.
  03-N-
qt26.2/
1-4
female/
8y
PBL/ fibroblasts de novo 46,XX in PBL
47,XX,+mar[14]/46,XX[45]
in fibroblasts
inv dup(3)(qterq26.2: :q26.2qter) n.a. skeletal abnormalities, limb stiffness, abnormal skin pigmentation, developmental delay {23; 32}  
  03-N-
qt26.3/
1-1
male/
adult?
bone marrow de novo
acquired
46,XY in PBL/ constitutional
50,XY,der(1)(qter→ q21::p36→qter),+8,+10,+13,+mar
inv dup(3)(qter→q26.3: :q26.3→qter) CGH,
subtelomere-FISH
Fanconi anemia {24}  
  03-N-
qt26.3/
2-1
female/
5y
PBL de novo 47,XX,+mar[27]/
46,XX[3]
inv dup(3)(qterq29: :q26.3qter) SKY, array CGH,
BAC-FISH
see below {30, 31, 37}  
Born after uneventful pregnancy; at birth normal growth values (50th centile). However, at birth diastasis recta, atrial septal defect, dysmorphic facies synophris, hirsutism, flat face, low nasal bridge, thin underlip, long philtrum) plus short 5th finger on both hands. Developmental delay. At 3.5y developmental quotient of 38-39. At 5y moderate to severe delay in psychomotor development. weight 16.6kg (10-25 centile), height 99cm (<3rd centile), OFC 50.2 cm (50-75th centile).
  03-N-
qt26.32/
1-1
female/
4y
skin fibroblasts de novo 47,XX,+mar[38]/
46,XX[12]

  inv dup(3)(:q28q26.32:q26.32q28:)
array: 177,68- 198,04 Mb

array-CGH see below {48; 57}  

developmental delay, speech abnormalities, congenital; cardiac defects, umbilical hernia, high arched palate, cubitus valgus, short; metacarpals and metatarsus, intermamilar increased distance, hirsutism, hypertrichosis, low set ears, hypopigmented streaks and whorls along the Blaschko's lines on face, trunk, legs, and arms

  03-N-
qt27.1/
1-1
male/
22y
PBL/
skin fibroblasts
n.a. 47,XY,+mar[30%]/
46,XY[70%]
(sSMC present in 6% of fibroblasts of hyper pigmented skin; absent in normal pigmented skin)
inv dup(3)(qterq27.1: :q27.1qter) all wcp probes; an all centromeric probe, cep3, 30 YACS along chromosome 3 progredient pigmentary coetaneous anomalies following the Blaschko lines since 10-12y of age {13; 18; 22; 32}  
  03-N-
qt27.2/
1-1
female/
1.5y
PBL de novo 47,XY,+mar[42]/
46,XY[17]
inv dup(3)(qterq27.2: :q27.2qter) pan-centromeric probe; telomeric probe; wcp3 subtel 3q; SKY see below {17} case 1; {18; 22; 32; 53}  
Birth by cesarean section due to breech presentation in week 39; birth weight at 75. centile; dislocated right hip; shallow acetabula fossa on the left At age 3 to 4 days, swirly areas of hyperpigmentation on her back, abdomen, thighs, and forearms were noted. At age 8 months, head circumference was at 75th centile, height and weight at 90th centile, face flat with depressed nasal bridge; bilateral preauricular pits; hypotonia; developmental delay. At 14 months seizures; scoliosis, far-sightedness and strabismus. At 7 years globally developmental delayed but socially interactive.
  03-N-
qt28/
1-1
female/
5y
PBL de novo? 47,XX,+mar[100%?] inv dup(3)(qterq28: :q28qter) an all centromeric probe,  midi, Sub-telomeric probes 3q and 14 YAC/BAC probes from 3q26-29 see below {15; 18; 22; 32}  
At 5y marked developmental delay and mild facial dysmorphism. At birth length 49cm, weight 2965 g, OFC 34 cm. At age of 8.5y height 131 cm, weight 37 kg (>97th centile); hypognathia, broad flat nasal root, abnormally shaped alae nasi; median upper lids with atypical epicanthus; slight hirsutism ; bilateral ichthyosiform hyperkeratosis of the palms and soles; slight muscular hypotonia and hyporeflexia. Perceptive skills and visuomotor coordination retarded corresponding to a developmental age of 3-3.5 years. At age of 8.5 years she cannot speak properly, searching for words, can recognize only between 10 and 15 letters, and is still not able to write.
                     

 

other 6 neocentromeric cases with involvement of chromosome 3 (no sSMC):

Maraschio P, Tupler R, Rossi E, Barbierato L, Uccellatore F, Rocchi M, Zuffardi O, Fraccaro M.
A novel mechanism for the origin of supernumerary marker chromosomes.
Hum Genet. 1996 Mar;97(3):382-6.

Gimelli G, Zuffardi O, Giglio S, Zeng C, He D.
CENP-G in neocentromeres and inactive centromeres.
Chromosoma. 2000;109(5):328-33.

Ventura M, Weigl S, Carbone L, Cardone MF, Misceo D, Teti M, D'Addabbo P, Wandall A, Bjorck E, de Jong PJ, She X, Eichler EE, Archidiacono N, Rocchi M.
Recurrent sites for new centromere seeding.
Genome Res. 2004 Sep;14(9):1696-1703. (case 2**)

Papenhausen P, Gadi I, Tepperberg J, Mowrey P, Singh-Kahlon P, Wisniewski L, Goodwin D
Trisomy 3q secondary to a terminal deletion/generation of a mirrorimage analphoid marker in a neonate. 
Am J Hum Genet. 2003; 73: Suppl:313 (Abstractno 841).

Gimelli G, Giorda R, Beri S, Gimelli S, Zuffardi O.
A large analphoid invdup(3)(q22.3qter) marker chromosome characterized by array-CGH in a child with malformations, mental retardation, ambiguous genitalia and Blaschko's lines.
Eur J Med Genet. 2007 Jul-Aug;50(4):264-73. (case 3**)

Tsuchiya KD, Opheim KE, Hannibal MC, Hing AV, Glass JA, Raff ML, Norwood T, Torchia BA.
Unexpected structural complexity of supernumerary marker chromosomes characterized by microarray comparative genomic hybridization
Molecular Cytogenetics 2008, 1:7 (case 1)

** = identical case

 

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  
  03-N-
IMB-
p25/
1-1
male/
4.5y
PBL de novo 46,XY,dup(3)(p25pter) n.a. see below {34; see also similar cases 40}  
moderate growth and mental retardation, muscular hypotonia, hypoplasia of the left kidney, a short neck, and a square-shaped face characterized by a broad and flat nasal bridge, slight epicanthus, and full cheeks, dysmorphic signs are less impressive, and developmental delay is relatively moderate
  03-N-
IMB-
q26.3/
1-1
male/
11y
PBL de novo 46,XY,invdup(3)(q29q26.3::q26.3q29),del(12)(p13.33)[56]/
46, XY[45]
wcp 3, D3S456011, subtel 12p autism, mental retardation, developmental delay; born with a clubfoot, {35}  
  03-N-
IMB-
q25.3/
1-1
female/
newborn
PBL de novo 46,XY,trp(3)(q25.3q29) wcp, BACs see below {36}  
The girl died at the age of 3.5 weeks due to her malformations. She demonstrated disproportionate short stature with short limbs, a prominent and hairy forehead, thick eyebrows, synophris, small upturned nose, full cheeks, micrognathia, and low set malformed and posteriorly rotated ears, short and webbed neck, hydrocephalus, Dandy-Walker malformation, spina bifida, complex heart defect (ventricular and atrial septal defect, malrotation, and interrupted aortic arch), omphalocoele, polycystic kidneys, postaxial polydactyly of left hand, and generalized hirsutism
  03-N-
IMB-
q29/
1-1
female/
9y
PBL de novo 46,XX. arr cgh dup(3)(q29) array CGH; i-FISH with involved clones see below {29}  
Born at 37 weeks of gestation. Pregnancy complicated by prolonged premature rupture of membranes at 29 weeks. Birth weight 1.78 kg, multiple gastro-intestinal abnormalities (tracheosephageal fistula, esophageal atresia, imperforate anus, Meckel diverticulum, malrotation). Abnormal segmented sacrum with hemi vertebra at S4. Patent foramen ovale. VATER association. At 2.5 years - after some surgical corrections - she done quite well and had no developmental delay. At 9 y - minor dysmorphism signs at hand, feet and face