PMID- 15264281
OWN - NLM
STAT- MEDLINE
DCOM- 20050218
LR  - 20200930
IS  - 1552-4825 (Print)
IS  - 1552-4825 (Linking)
VI  - 128A
IP  - 4
DP  - 2004 Aug 1
TI  - Subtelomere FISH in 50 children with mental retardation and minor anomalies, 
      identified by a checklist, detects 10 rearrangements including a de novo balanced 
      translocation of chromosomes 17p13.3 and 20q13.33.
PG  - 364-73
AB  - Submicroscopic or subtle aneusomies at the chromosome ends, typically diagnosed 
      by subtelomere fluorescence in situ hybridization (FISH), are a significant cause 
      of idiopathic mental retardation (MR). Some 20 subtelomere studies, including 
      more than 2,500 subjects, have been reported. The studies are not directly 
      comparable because different techniques and patient ascertainment criteria were 
      used, but an analysis of 14 studies showed that aberrations were detected in 97 
      out of 1,718 patients (5.8%, range 2-29%; 95% confidence interval (CI) 
      4.60-6.84%). We performed a subtelomere FISH study of 50 unrelated children 
      ascertained by a checklist that evaluates MR or developmental delay, dysmorphism, 
      growth defect, and abnormal pedigree and found 10 bona fide causal rearrangements 
      (detection rate 20%, 95% CI 10-33.7%). The findings included five unbalanced 
      familial translocations or inversions, two unbalanced de novo translocations, and 
      two de novo deletions. Patient 5 showed multiple anomalies (large head, vision 
      defect, omphalocele, heart defect, enlarged kidneys, moderate MR, speech defect, 
      mild transient homocysteinemia) and a de novo balanced translocation of 
      chromosomes 17p13.3 and 20q13.33. The report of a subtelomeric balanced 
      rearrangement associated with a disease phenotype is a novel one. FISH mapping 
      using panels of overlapping BAC clones identified a number of candidate genes at 
      or near his breakpoints, including ASPA, TRPV3, TRPV1, and CTNS at 17p13.3, and 
      three genes of unknown function at 20q13.33. Only the homocysteinemia could be 
      speculatively linked to one of these genes (CTNS, the gene for cystinosis). Three 
      within the subset of 16 children (18.8%) with mild (IQ, 50-69) or unspecified 
      degree of MR tested positive, suggesting that the checklist approach could be 
      especially useful within this group of patients.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Walter, Sabine
AU  - Walter S
AD  - Institute of Clinical Genetics, Dresden University of Technology, Dresden, 
      Germany.
FAU - Sandig, Klaus
AU  - Sandig K
FAU - Hinkel, Georg K
AU  - Hinkel GK
FAU - Mitulla, Beate
AU  - Mitulla B
FAU - Ounap, Katrin
AU  - Ounap K
FAU - Sims, Giles
AU  - Sims G
FAU - Sitska, Mari
AU  - Sitska M
FAU - Utermann, Barbara
AU  - Utermann B
FAU - Viertel, Petra
AU  - Viertel P
FAU - Kalscheuer, Vera
AU  - Kalscheuer V
FAU - Bartsch, Oliver
AU  - Bartsch O
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Child, Preschool
MH  - *Chromosome Aberrations
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 17
MH  - *Chromosomes, Human, Pair 20
MH  - Cytogenetic Analysis
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Infant, Newborn
MH  - Intellectual Disability/*genetics
MH  - Male
MH  - Phenotype
MH  - Telomere
MH  - *Translocation, Genetic
EDAT- 2004/07/21 05:00
MHDA- 2005/02/19 09:00
CRDT- 2004/07/21 05:00
PHST- 2004/07/21 05:00 [pubmed]
PHST- 2005/02/19 09:00 [medline]
PHST- 2004/07/21 05:00 [entrez]
AID - 10.1002/ajmg.a.30160 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2004 Aug 1;128A(4):364-73. doi: 10.1002/ajmg.a.30160.