Clinical and Genetic Analysis of Alopecia and Ectodermal Dysplasia in Three Consanguineous Families

Abstract

Skin, via its interaction with the external environment, has a protective role along with the distinctive functions oflubrication and thermoregulation. The skin appendages that includes the teeth, nails, hair and sweat glands share common functions like immune surveillance, epidermal barrier, and role in pigmentation and defense mechanism in the skin. Human hair is an utter epitome of aesthetics in our culture. Approximately 5 billion hair are present in humans that act as an outer protective covering. The defects in the expression of the genes that are particularly present in the human hair follicle are associated with the congenital hair loss disorders (CHLD) or Alopecia. Moreover, the phenotypes involving the dry skin, scaling and hyperkeratosis comes under the large group disorders termed as palmoplantar keratoderma (PPK). The molecular characterization of the clinical features underlying PPK have developed a concrete understanding by identifying pathogenic mutations in the genes that have crucial role in skin barrier formation. The study; presented in the dissertation, potentially investigated the clinical and molecular characterization of three families (A, B, and C) of the Pakistani origin exhibiting consanguineous unions, segregating different types of autosomal recessive congenital hair and ectodermal dysplasia. Family A and B were sampled from Khyber Pakhtunkhwa while family C was sampled from Baluchistan. Family A presented isolated fonn of alopecia, family B inherited syndromic form of alopecia while family C showed features of PPK with hyperkeratotic plaques on the skin surface of palms, soles ankles, and between the digits. With the aim of establishing the linkage analysis in all the three families, genotyping using the micro satellite markers was performed. The affected individuals present in all the three families were found to be heterozygous for different parental alleles' combinations thus, excluding the families for linkage to pre-existing genes/loci. Furthermore, in thc family Band C, Sanger sequencing of single-exon containing genes, GlB6 and GlA] , was performed by dideoxy chain termination method. Analysis of the results failed to show any phenotypic variant, suggesting the involvement of either the regulatory sequences of the genes or another unknown gene present in the same region.