title: Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation.
abstract: Hair-nail ectodermal dysplasia (HNED; OMIM 602032) constitutes a rare subgroup of ectodermal dysplasias characterised by onychodystrophy, hypotrichosis and brittle hair. We identified a large consanguineous Pakistani family with four siblings affected by a congenital autosomal recessive form of the disease. Based on previous genetic findings in HNED we performed linkage analysis in the family using chromosome 12 markers. A genetic linkage analysis revealed a lod score of 2.92 ( = 0.0) at locus D12S368, indicating the disease gene to be located on chromosome 12. Candidate genes on chromosome 12, including the KRTHB5 gene and four additional keratin II genes, were sequenced in affected family members. Sequence analysis of the coding regions of keratin KRTHB5 gene, previously associated with a distinct clinical form of hair-nail dysplasia, revealed normal coding regions. Our study confirms linkage of a variant clinical form of hair-nail ectodermal dysplasia to chromosome 12 without any mutation in the coding sequences of the KRTHB5 gene. The results suggest this family to have either a non-coding mutation in the KRTHB5 gene, or a mutation in a yet unknown gene within the linked region on chromosome 12.
authors.affiliation: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Rasool
authors.forename: Sadia
authors.initials: S
authors.lastname: Nawaz
authors.forename: Aysha
authors.initials: A
authors.lastname: Azhar
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Baig
authors.forename: Joakim
authors.initials: J
authors.lastname: Klar
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000328:Adult; D002881:Chromosomes, Human, Pair 12; D003241:Consanguinity; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D006201:Hair Diseases / Q000235:genetics*; D006801:Humans; D053564:Keratins, Hair-Specific / Q000235:genetics*; D053531:Keratins, Type II / Q000235:genetics*; D008126:Lod Score; D008297:Male; D009154:Mutation; D009260:Nail Diseases / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: C507604:KRT85 protein, human; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II