title: A novel mutation in lysophosphatidic acid receptor 6 gene in autosomal recessive hypotrichosis and evidence for a founder effect.
abstract: Mutations in the lysophosphatidic acid receptor 6 (LPAR6) gene cause localized autosomal recessive hypotrichosis. We report six consanguineous families from Pakistan with segregating hypotrichosis localized to the scalp. Genetic investigation using polymorphic microsatellite markers revealed homozygosity spanning the LAH3 locus on chromosome 13 in affected individuals of all six families. Sequence analysis of the LPAR6 gene showed a novel insertion resulting in a frameshift and a premature termination (p.I194FfsX11) in affected members of one family. In the remaining five families we identified a previously described missense mutation (p.G146R) in a homozygous state in affected members. The closest flanking polymorphic marker showed an identical allele size in the five families segregating with the p.G146R mutation, supporting a single origin of this variation. These findings extend the spectrum of known LPAR6 mutations and suggest a founder effect of the p.G146R mutation in the Pakistani population.
authors.affiliation: Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan.
authors.forename: Aysha
authors.initials: A
authors.lastname: Azhar
authors.forename: Muhammad
authors.initials: M
authors.lastname: Tariq
authors.forename: Shahid Mahmood
authors.initials: SM
authors.lastname: Baig
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
authors.forename: Joakim
authors.initials: J
authors.lastname: Klar
mesh_terms: D000328:Adult; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*
chemical_list: C545560:LPAR6 protein, human; D049368:Receptors, Lysophosphatidic Acid