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.
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Article: Localization of a novel autosomal recessive hypotrichosis locus (LAH3) to chromosome 13q14.11-q21.32.
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- "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. Affected male individuals have normal beard hair   . To date, three similar forms of autosomal recessive hypotrichosis (LAH1, LAH2, LAH3) have been reported. "
ABSTRACT: Autosomal recessive hypotrishosis (LAH2) is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. However, affected male individuals have normal beard hair. Mutations in lipase H (LIPH) gene, located on chromosome 3q26.33, have been shown to be responsible for LAH2 type of hypotrichosis. To search for pathogenic mutations in LIPH gene at LAH2 locus in Pakistani families demonstrating autosomal recessive hypotrichosis. In the present study we have ascertained two large unrelated consanguineous Pakistani families (A and B) inherited autosomal recessive form of hypotrichosis. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene at LAH2 locus on chromosome 3q26.33. These families were then subjected to direct sequencing of the LIPH gene. Sequence analysis of the LIPH gene revealed two novel missense mutations (c.2T>C; p.M1T and c.322T>C; p.W108R) in the two families. The mutations reported here are the first missense mutations identified in the LIPH gene, which extend the body of evidences implicating the LIPH gene in the pathogenesis of human hereditary hair loss.Journal of dermatological science 04/2009; 54(1):12-6. DOI:10.1016/j.jdermsci.2008.12.001 · 3.34 Impact Factor
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ABSTRACT: Hypotrichosis simplex is a group of nonsyndromic human alopecias. We mapped an autosomal recessive form of this disorder to chromosome 13q14.11-13q21.33, and identified homozygous truncating mutations in P2RY5, which encodes an orphan G protein-coupled receptor. Furthermore, we identified oleoyl-L-alpha-lysophosphatidic acid (LPA), a bioactive lipid, as a ligand for P2Y5 in reporter gene and radioligand binding experiments. Homology and studies of signaling transduction pathways suggest that P2Y5 is a member of a subgroup of LPA receptors, which also includes LPA4 and LPA5. Our study is the first to implicate a G protein-coupled receptor as essential for and specific to the maintenance of human hair growth. This finding may provide opportunities for new therapeutic approaches to the treatment of hair loss in humans.Nature Genetics 04/2008; 40(3):329-34. DOI:10.1038/ng.84 · 29.65 Impact Factor
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ABSTRACT: Autosomal recessive hypotrichosis is a rare hereditary disorder characterized by sparse hair on scalp and rest of the body of affected subjects. Recently, three clinically similar autosomal recessive forms of hypotrichosis [localized autosomal recessive hypotrichosis (LAH)1], LAH2 and LAH3 have been mapped on chromosomes 18q12.1, 3q27.3, and 13q14.11-q21.32, respectively. For these three loci, two genes DSG4 for LAH1 and LIPH for LAH2 have been identified. To date, only five mutations in DSG4 and two in LIPH genes have been reported. In this study, we have ascertained two large unrelated consanguineous Pakistani families with autosomal recessive form of hypotrichosis. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene on chromosome 3q27. Sequence analysis of the gene in the affected subjects from both the families revealed a novel deletion mutation in exon 5 (c.659-660delTA) causing frameshift and downstream premature termination codon. All the three mutations identified in the LIPH gene, including the one in this study, are deletion mutations.Clinical Genetics 05/2008; 74(2):184-8. DOI:10.1111/j.1399-0004.2008.01011.x · 3.65 Impact Factor