PMID- 11280955
OWN - NLM
STAT- MEDLINE
DCOM- 20010809
LR  - 20220210
IS  - 1098-3600 (Print)
IS  - 1098-3600 (Linking)
VI  - 3
IP  - 2
DP  - 2001 Mar-Apr
TI  - Down syndrome congenital heart disease: a narrowed region and a candidate gene.
PG  - 91-101
AB  - PURPOSE: Down syndrome (DS) is a major cause of congenital heart disease (CHD) 
      and the most frequent known cause of atrioventricular septal defects (AVSDs). 
      Molecular studies of rare individuals with CHD and partial duplications of 
      chromosome 21 established a candidate region that included D21S55 through the 
      telomere. We now report human molecular and cardiac data that narrow the DS-CHD 
      region, excluding two candidate regions, and propose DSCAM (Down syndrome cell 
      adhesion molecule) as a candidate gene. METHODS: A panel of 19 individuals with 
      partial trisomy 21 was evaluated using quantitative Southern blot dosage analysis 
      and fluorescence in situ hybridization (FISH) with subsets of 32 BACs spanning 
      the region defined by D21S16 (21q11.2) through the telomere. These BACs span the 
      molecular markers D21S55, ERG, ETS2, MX1/2, collagen XVIII and collagen VI A1/A2. 
      Fourteen individuals are duplicated for the candidate region, of whom eight (57%) 
      have the characteristic spectrum of DS-CHD. RESULTS: Combining the results from 
      these eight individuals suggests the candidate region for DS-CHD is demarcated by 
      D21S3 (defined by ventricular septal defect), through PFKL (defined by tetralogy 
      of Fallot). CONCLUSIONS: These data suggest that the presence of three copies of 
      gene(s) from the region is sufficient for the production of subsets of DS-CHD. 
      This region does not include genes located near D21S55, previously proposed as a 
      "DS critical region," or the genes encoding collagens VI and XVIII. Of the 
      potential gene candidates in the narrowed DS-CHD region, DSCAM is notable in that 
      it encodes a cell adhesion molecule, spans more than 840 kb of the candidate 
      region, and is expressed in the heart during cardiac development. Given these 
      properties, we propose DSCAM as a candidate for DS-CHD.
FAU - Barlow, G M
AU  - Barlow GM
AD  - Department of Medical Genetics, Cedars-Sinai Medical Center and UCLA, Los 
      Angeles, California, USA.
FAU - Chen, X N
AU  - Chen XN
FAU - Shi, Z Y
AU  - Shi ZY
FAU - Lyons, G E
AU  - Lyons GE
FAU - Kurnit, D M
AU  - Kurnit DM
FAU - Celle, L
AU  - Celle L
FAU - Spinner, N B
AU  - Spinner NB
FAU - Zackai, E
AU  - Zackai E
FAU - Pettenati, M J
AU  - Pettenati MJ
FAU - Van Riper, A J
AU  - Van Riper AJ
FAU - Vekemans, M J
AU  - Vekemans MJ
FAU - Mjaatvedt, C H
AU  - Mjaatvedt CH
FAU - Korenberg, J R
AU  - Korenberg JR
LA  - eng
GR  - HD17449/HD/NICHD NIH HHS/United States
GR  - HL50025/HL/NHLBI NIH HHS/United States
GR  - HL61033/HL/NHLBI NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genet Med
JT  - Genetics in medicine : official journal of the American College of Medical 
      Genetics
JID - 9815831
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DSCAM protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proteins)
SB  - IM
MH  - Blotting, Southern
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/genetics/physiology
MH  - Child, Preschool
MH  - *Chromosome Mapping
MH  - Chromosomes, Artificial, Bacterial
MH  - Chromosomes, Human, Pair 21
MH  - Down Syndrome/*complications/*genetics
MH  - Facies
MH  - Female
MH  - Genotype
MH  - Heart Defects, Congenital/*complications/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Karyotyping
MH  - Male
MH  - Membrane Proteins
MH  - Models, Genetic
MH  - Phenotype
MH  - Pregnancy
MH  - Proteins/chemistry/*genetics/metabolism
EDAT- 2001/04/03 10:00
MHDA- 2001/08/10 10:01
CRDT- 2001/04/03 10:00
PHST- 2001/04/03 10:00 [pubmed]
PHST- 2001/08/10 10:01 [medline]
PHST- 2001/04/03 10:00 [entrez]
AID - S1098-3600(21)00873-X [pii]
AID - 10.1097/00125817-200103000-00002 [doi]
PST - ppublish
SO  - Genet Med. 2001 Mar-Apr;3(2):91-101. doi: 10.1097/00125817-200103000-00002.