A second autosomal split hand/split foot locus maps to chromosome 10q24-q25

Area of Science:

• Human Genetics
• Developmental Biology
• Medical Genetics

Background:

• Ectrodactyly, or split hand/split foot malformation (SHSF), is a congenital limb defect with known genetic heterogeneity.
• Existing identified loci include SHFM1 (autosomal) and SHFM2 (X-linked), but multiple autosomal loci are suspected.

Purpose of the Study:

• To investigate a potential new autosomal locus for SHSF on chromosome 10q.
• To map the precise location of this novel SHSF locus.

Main Methods:

• Utilized microsatellite markers for linkage analysis in a large family with autosomal dominant SHSF.
• Analyzed an infant with ectrodactyly and an unbalanced translocation involving 10q25.2-qter.
• Performed recombination haplotype analysis to define the critical region.

Main Results:

• Identified a novel SHSF locus, designated SHFM3, on chromosome 10q25.
• Established the locus within a 9 cM interval between markers D10S541 and D10S574.
• Achieved a maximum LOD score of 4.21 at theta = 0.00 with marker D10S583.

Conclusions:

• Chromosome 10q25 harbors a second autosomal locus responsible for SHSF.
• The identification of SHFM3 contributes to understanding the genetic basis of limb malformations.