Localization of a novel autosomal recessive hypotrichosis locus (LAH3) to chromosome 13q14.11-q21.32.
ABSTRACT Autosomal recessive hypotrichosis is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. Previously, for this form of hypotrichosis, two loci LAH (localized hereditary hypotrichosis) and AH (autosomal recessive hereditary hypotrichosis) have been mapped on chromosome 18q12.1 and 3q27.2, respectively. In the study presented here, we report the localization of a third locus for autosomal recessive form of hypotrichosis in two large Pakistani families. The patients in the two families exhibited typical features of the hereditary hypotrichosis. Genome scan using polymorphic microsatellite markers mapped the gene on chromosome 13q14.11-q21.32. A maximum combined two-point logarithm of odds (LOD) score of 4.79 at theta= 0.0 was obtained for several markers. Multipoint linkage analysis resulted in a maximum LOD score of 5.9, which further supports the linkage. Haplotype analysis defined the linkage interval of 17.35 cM flanked by markers D13S325 and D13S1231 according to the Rutgers combined linkage-physical map. This region contains 24.41 Mb according to the build 36 of the human genome sequence-based physical map.
[Show abstract] [Hide abstract]
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.European journal of dermatology: EJD 04/2012; 22(4):464-6. DOI:10.1684/ejd.2012.1731 · 1.95 Impact Factor
Acta Dermato-Venereologica 06/2011; 91(4):486-8. DOI:10.2340/00015555-1095 · 4.24 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Mutations in the lipase member H (LIPH) gene cause autosomal recessive hypotrichosis with woolly hair. We report herein on five consanguineous families from Pakistan segregating hypotrichosis and woolly hair. Genetic investigation using polymorphic microsatellite markers revealed homozygosity for a region spanning the HYPT7 locus on chromosome 3 in affected individuals of all five families. Sequence analysis of the LIPH gene revealed a novel nonsense mutation (p.Arg260X) associated with hypotrichosis without woolly hair in one family. In the remaining four families we identified previously described mutations in a homozygous state in affected members. These findings extend the spectrum of known LIPH mutations in the Pakistani population.Scientific Reports 10/2012; 2:730. DOI:10.1038/srep00730 · 5.08 Impact Factor