title: A large duplication in LIPH underlies autosomal recessive hypotrichosis simplex in four Middle Eastern families.
abstract: Autosomal recessive hypotrichosis simplex (ARHS) manifests with paucity of hair appearing during early childhood. We assessed four affected families. We initially genotyped three of these families for a panel of microsatellite markers spanning all ARHS-associated loci and obtained data suggesting linkage to 3q27, encompassing LIPH, which had previously been shown to be associated with ARHS. Accordingly, a homozygous duplication mutation in exon 2 of this gene (c.280_369dup; p.Gly94_Lys123dup) was found to segregate with the disease in all the families. Through the identification of the first duplication mutation in the human LIPH gene, we provide further evidence supporting a role for the phospholipase signalling pathway in hair growth and differentiation.
authors.affiliation: Laboratory of Molecular Dermatology, Department of Dermatology, Rambam Medical Center, Rambam Health Care Campus, POB 9602, 31096, Haifa, Israel.
authors.forename: Sagi
authors.initials: S
authors.lastname: Nahum
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Pasternack
authors.forename: Jana
authors.initials: J
authors.lastname: Pforr
authors.forename: Margarita
authors.initials: M
authors.lastname: Indelman
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollnik
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Arne
authors.initials: A
authors.lastname: König
authors.forename: Ziyad
authors.initials: Z
authors.lastname: Khamaysi
authors.forename: Regina C
authors.initials: RC
authors.lastname: Betz
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D018912:Arabs; D002648:Child; D025063:Chromosome Disorders / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002893:Chromosomes, Human, Pair 3; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D020440:Gene Duplication; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006197:Hair / Q000002:abnormalities / Q000254:growth & development / Q000473:pathology; D018859:Hair Follicle / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007039:Hypotrichosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D007557:Israel; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic; D014421:Turkey
chemical_list: C504173:LIPC protein, human; D008049:Lipase