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- CHROMOSOME #3 -
NEOCENTRIC
are based on the bias, that mainly clinically aberrant cases are studied and reported in literature!
| UPD (uniparental disomy) cases: | UPD(3)mat | UPD(3)pat | UPD(3)mat or pat |
| 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; aCGH | 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/ 1-1 |
male/ 1y |
PBL skin fibros |
de novo |
47,XY,+mar[30-45%]/ 46,XY[70-55%] |
r(3)(::q26.1→q27.3::) | aCGH; wcp 4; locusspecific probe | mild ID, DYS; proximal polydactyly of hands; hernia, cryptochidism; lenght at 14y at 18th centile | {58} case 1 |
| 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)(qter→q26.2: :q26.2→qter) (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)(qter→q26.2: :q26.2→qter) | 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)(qter→q26.2: :q26.2→qter) | 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)(qter→q26.2: :q26.2→qter) | n.a. | skeletal abnormalities, limb stiffness, abnormal skin pigmentation, developmental delay | {23; 32} |
| 03- N- qt26.3/ 2-1 |
female/ 5y |
PBL | de novo | 47,XX,+mar[27]/ 46,XX[3] |
inv dup(3)(qter→q29: :q26.3→qter) | 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- qt26.31/ 1-1 |
male/ prenatal |
AF |
de novo | 47,XY,+mar[7]/ 46,XY[38] |
inv
dup(3)(qter→q26.31: :q26.31→qter) break in (hg19): 172,86 Mb |
aCGH |
nasal bone
hypoplasia, TOP |
{62} case 3 |
| 03- N- qt26.32/ 1-1 |
female/ 4y |
skin fibroblasts | de novo | 47,XX,+mar[38]/ 46,XX[12] |
inv
dup(3)(:q28→q26.32:q26.32→q28:) array: 177,68- 198,04 Mb |
aCGH | 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)(qter→q27.1: :q27.1→qter) | 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)(qter→q27.2: :q27.2→qter) | 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)(qter→q28: :q28→qter) | 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. | ||||||||
| 03- N- qt28/ 1-2 |
male/ 10y |
PBL | de novo? | 47,XY,+mar[6]/ 46,XY[4] |
inv
dup(3)(qter→q28: :q28→qter) size 7.2 Mb |
aCGH | DD,
accelarated bome age, ADHS |
{0} provided by Dr. Schmidt,
Gelnhausen, Germany |
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**) = identical case as above! 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) |
| 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- qt26/ 1-1 |
male/ 50y |
abdominal wall metastasis of a lung sarcanoid carcinoma | de novo; acquired | GTG and
FISH result combined: 67~73,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 {25} aCGH |
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)(qter→q2?6: :q2?6→qter) | 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)(qter→q26: :q26→qter) | wcp and FISH with different probes | T-cell lymphoma - case maybe the same as 03-N-q26/2-1. | {28} |
| 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} |
| case no. |
gender/ age at diagnosis |
studied material |
de novo/ inherited |
GTG-banding and final FISH
result |
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,inv
dup(3)(q29→q26.3::q26.3→q29), 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) | aCGH; 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 | ||||||||
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