Genetic mapping of an autosomal recessive postaxial polydactyly type A to chromosome 13q13.3–q21.2 and screening of the candidate genes

Abstract

Postaxial Polydactyly (PAP) is characterized by fifth digit duplication in hands and/or feet. Two types of PAP including PAP-A, representing the development of well-formed extra digit, and PAP-B, representing the presence of rudimentary fifth digit, have been described. Both isolated and syndromic forms of PAP have been reported. Isolated forms of PAP usually segregate as an autosomal dominant trait and to date four loci have been identified. In the present study, we have described mapping of the first locus of autosomal recessive PAP type A on chromosome 13q13.3-13q21.2 in a consanguineous Pakistani family. Using polymorphic microsatellite markers, the disease locus was mapped to a 17.87-cM (21.13 Mb) region flanked by markers D13S1288 and D13S632, on chromosome 13q13.3-13q21.2. A maximum multipoint LOD score of 3.84 was obtained with several markers along the disease interval. DNA sequence analysis of exons and splice-junction sites of ten candidate genes (CHM-I, TSC22D1, FOXO1, DIAPH3, CCDC122, CKAP2, SUGT1, RANKL, LPAR6, C13ORF31) did not reveal potentially causal variants.

Whole exome sequencing identified a novel zinc-finger geneZNF141associated with autosomal recessive postaxial polydactyly type A

“…Affected individuals of the family, presented here, showed well-formed six digits in both hands and feet. This form of autosomal recessive PAP is clearly distinct from the one we described previously,13 as it clearly maps in a different chromosomal location. Also, the present study showed a novel phenotype of wide and deviated fifth finger on at least one hand.…”

“…Affected individuals in both of these families had well developed sixth digits. In the family reported by Umm-e-Kalsoom et al 13 an additional feature of hallux valgus deformity was observed in one of the affected individual. Affected individuals of the family, presented here, showed well-formed six digits in both hands and feet.…”

“…In the present study we have presented a family segregating PAP type A in an autosomal recessive manner. Previously, only two families segregating PAP in autosomal recessive manner had been reported 13 32. Umm-e-Kalsoom et al 13 further reported mapping of the PAP type A in their family on chromosome 13q13.3-q21.2.…”

“…Previously, only two families segregating PAP in autosomal recessive manner had been reported 13 32. Umm-e-Kalsoom et al 13 further reported mapping of the PAP type A in their family on chromosome 13q13.3-q21.2. Affected individuals in both of these families had well developed sixth digits.…”

“…Recently we reported mapping of the first locus of autosomal recessive PAP type A in a consanguineous Pakistani family on chromosome 13q13.3-q21.2 13. Here, we present a second consanguineous Pakistani family segregating PAP type A.…”