Frequency of genomic rearrangements involving the SHFM3 locus at chromosome 10q24 in syndromic and non-syndromic split-hand/foot malformation

Autor: Chad T. Morgan, David B. Everman, Michael J. Bamshad, Jacquelyn Roberson, Charles E. Schwartz, Randall S. Colby, Connie Schrander-Stumpel, Mary E. Laughridge, Stylianos E. Antonarakis, Hans van Bokhoven, Fiorella Gurrieri, Katie Clarkson, Robert Lyle, A. Micheil Innes
Rok vydání: 2006
Předmět:
Foot Deformities
Congenital/diagnosis/ genetics
Ectrodactyly
Polymerase Chain Reaction/methods
Foot Deformities
Congenital
Genetics and epigenetic pathways of disease [NCMLS 6]
Genetic Linkage
F-Box Proteins/ genetics
Locus (genetics)
Biology
Polymerase Chain Reaction
Chromosomes
Human
Pair 10/ genetics
Gene Frequency
Gene mapping
Genetic linkage
Gene Duplication
Chromosome regions
TP63
Genetics
medicine
Abnormalities
Multiple/diagnosis/ genetics
Humans
Abnormalities
Multiple
Syndactyly
Genetics (clinical)
ddc:616
Gene Rearrangement
Hand Deformities
Congenital/diagnosis/ genetics
Chromosomes
Human
Pair 10
F-Box Proteins
Linkage (Genetics)
Chromosome Mapping
Syndrome
Gene rearrangement
medicine.disease
Electrophoresis
Gel
Pulsed-Field
Genetic defects of metabolism [UMCN 5.1]
Hand Deformities
Congenital
Functional Neurogenomics [DCN 2]
Zdroj: American Journal of Medical Genetics. Part A, 140, 1375-83
American Journal of Medical Genetics. Part A, 140, 13, pp. 1375-83
American Journal of Medical Genetics. A, Vol. 140, No 13 (2006) pp. 1375-1383
ISSN: 1552-4825
Popis: Contains fulltext : 50290.pdf (Publisher’s version ) (Closed access) Split-hand/foot malformation (SHFM), or ectrodactyly, is characterized by underdeveloped or absent central digital rays, clefts of the hands and feet, and variable syndactyly of the remaining digits. SHFM occurs as both an isolated finding and a component of many syndromes. SHFM is a heterogeneous condition caused by multiple loci, including SHFM1 (chromosome region 7q21-q22), SHFM2 (Xq26), SHFM3 (10q24), SHFM4 (3q27), and SHFM5 (2q31). Mutations in TP63 at the SHFM4 locus are known to underlie both syndromic and non-syndromic forms SHFM, but the causes of most non-syndromic SHFM cases remain unknown. The recent identification of submicroscopic tandem chromosome duplications affecting the SHFM3 locus in seven families with non-syndromic SHFM has helped to further unravel the molecular basis of this malformation. In our ongoing studies of the SHFM3 locus in 44 additional cases of syndromic and non-syndromic SHFM, we have identified similar chromosome rearrangements in eight additional cases (18%), using pulsed-field gel electrophoresis (PFGE). We have also utilized real-time quantitative PCR (qPCR) to test for the duplications. Seven of the cases with rearrangements were non-syndromic. The current findings bring the total of SHFM3-associated cases with chromosome rearrangements to 15, which constitute 29% (15 of 51) of the cases screened to date. This includes 9 of 9 cases (100%) with known linkage to the SHFM3 locus, all of whom have non-syndromic SHFM, and 6 of 42 additional cases (14%), four of whom have non-syndromic SHFM. Thus, SHFM3 abnormalities underlie a substantial proportion of SHFM cases and appear to be a more frequent cause of non-syndromic SHFM than mutations in TP63.
Databáze: OpenAIRE
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