RESUMO
To characterize the disease causing mutation in a large consanguineous Pakistani family with severe Mal de Meleda [MDM] or keratosis palmoplantaris transgrediens, a rare autosomal recessive skin disorder. Single nucleotide polymorphism [SNPs] genotyping was performed using the GeneChip Mapping 250K array [Affymetrix]. Homozygosity mapping and sorting of genomic regions were performed with dedicated software called AutoSNPa. Selected regions were further investigated by genotyping with microsatellite markers derived from known and novel polymorphic repeats. Two-point LOD score calculation was performed by using the MLINK of Fastlink computer package. All three coding exons of ARS [component B] gene were amplified by PCR and sequenced. Sequencing of all the coding exons of ARS [component B] gene in the affected individuals revealed a recurrent missense mutation in exon 3 at base pair 256 from Guanine to Alanine [256G>A] and as a result the amino acid Glycine is replaced by Arginine at position 86 [G86R]. This finding will facilitate control of affected MDM births in the Pakistani families