Microarray based analysis of 3p25-p26 deletions (3p- syndrome).
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 approximately 6 to 12 Mb. Assuming complete penetrance, a candidate critical region for a CHD susceptibility gene was refined to approximately 200 kb and a candidate critical region for mental retardation was mapped to an approximately 1 Mb interval containing SRGAP3 but other 3p neurodevelopmental 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.
Shuib
Salwati
S
Department of Medical and Molecular Genetics, University of Birmingham, Birmingham, UK.
McMullan
Dominic
D
Rattenberry
Eleanor
E
Barber
Richard M
RM
Rahman
Fatimah
F
Zatyka
Malgosia
M
Chapman
Cyril
C
Macdonald
Fiona
F
Latif
Farida
F
Davison
Val
V
Maher
Eamonn R
ER
D002648:Child; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome
D020690:GTPase-Activating Proteins; C465659:SRGAP3 protein, human