TY - JOUR
T1 - Microarray Based Analysis of 3p25-p26 Deletions (3p-Syndrome)
AU - Shuib, S
AU - McMullan, D
AU - Rattenberry, E
AU - Barber, RM
AU - Rahman, F
AU - Zatyka, Malgorzata
AU - Chapman, Cyril
AU - MacDonald, Fiona
AU - Latif, Farida
AU - Davison, V
AU - Maher, Eamonn
PY - 2009/10/1
Y1 - 2009/10/1
N2 - Distal deletion of chromosome 3p25-pter (3p- syndrome) produces a distinct clinical syndrome characterized by low birth weight, mental retardation, telecanthus, ptosis, and micrognathia. Congenital heart disease (CHD), typically atrioventricular septal defect (AVSD) occurs in about a third of patients. Previously we reported on an association between the presence of CHD and the proximal extent of the deletion such that a CHD susceptibility gene was mapped between D3S1263 and D3S3594. In addition, we and others have suggested several candidate genes for the psychomotor retardation usually seen with constitutional 3p25 deletions. In order to further investigate genotype-phenotype correlations in 3p- syndrome we analyzed 14 patients with cytogenetically detectable deletions of 3p25 (including one patient with a normal phenotype) using Affymetrix 250K SNP microarrays. Deletion size varied from similar to 6 to 12 Mb. Assuming complete penetrance, a candidate critical region for a CHD susceptibility gene was refined to similar to 200 kb and a candidate critical region for mental retardation was mapped to an similar to 1 Mb interval containing SRGAP3 but other 3p neuro-developmental genes including CHL1, CNTN4, LRRN1, and ITPR1 mapped outside the candidate critical interval. We suggest that current evidence suggests that SRGAP3 is the major determinant of mental retardation in distal 3p deletions. (c) 2009 Wiley-Liss, Inc.
AB - Distal deletion of chromosome 3p25-pter (3p- syndrome) produces a distinct clinical syndrome characterized by low birth weight, mental retardation, telecanthus, ptosis, and micrognathia. Congenital heart disease (CHD), typically atrioventricular septal defect (AVSD) occurs in about a third of patients. Previously we reported on an association between the presence of CHD and the proximal extent of the deletion such that a CHD susceptibility gene was mapped between D3S1263 and D3S3594. In addition, we and others have suggested several candidate genes for the psychomotor retardation usually seen with constitutional 3p25 deletions. In order to further investigate genotype-phenotype correlations in 3p- syndrome we analyzed 14 patients with cytogenetically detectable deletions of 3p25 (including one patient with a normal phenotype) using Affymetrix 250K SNP microarrays. Deletion size varied from similar to 6 to 12 Mb. Assuming complete penetrance, a candidate critical region for a CHD susceptibility gene was refined to similar to 200 kb and a candidate critical region for mental retardation was mapped to an similar to 1 Mb interval containing SRGAP3 but other 3p neuro-developmental genes including CHL1, CNTN4, LRRN1, and ITPR1 mapped outside the candidate critical interval. We suggest that current evidence suggests that SRGAP3 is the major determinant of mental retardation in distal 3p deletions. (c) 2009 Wiley-Liss, Inc.
KW - deletion
KW - renal cell carcinoma
KW - gene deletion
KW - Von Hippel-Lindau syndrome
KW - microarray
KW - chromosome 3
KW - exon
U2 - 10.1002/ajmg.a.32824
DO - 10.1002/ajmg.a.32824
M3 - Article
C2 - 19760623
SN - 1552-4833
VL - 149A
SP - 2099
EP - 2105
JO - American Journal of Medical Genetics Part A
JF - American Journal of Medical Genetics Part A
IS - 10
ER -