title: Autosomal Recessive Hypotrichosis with Woolly Hair Caused by a Mutation in the Keratin 25 Gene Expressed in Hair Follicles.
abstract: Hypotrichosis is an abnormal condition characterized by decreased hair density and various defects in hair structure and growth patterns. In particular, in woolly hair, hypotrichosis is characterized by a tightly curled structure and abnormal growth. In this study, we present a detailed comparative examination of individuals affected by autosomal-recessive hypotrichosis (ARH), which distinguishes two types of ARH. Earlier, we demonstrated that exon 4 deletion in the lipase H gene caused an ARH (hypotrichosis 7; MIM: 604379) in populations of the Volga-Ural region of Russia. Screening for this mutation in all affected individuals revealed its presence only in the group with the hypotrichosis 7 phenotype. Other patients formed a separate group of woolly hair-associated ARH, with a homozygous missense mutation c.712G>T (p.Val238Leu) in a highly conserved position of type I keratin KRT25 (K25). Haplotype analysis indicated a founder effect. An expression study in the HaCaT cell line demonstrated a deleterious effect of the p.Val238Leu mutation on the formation of keratin intermediate filaments. Hence, we have identified a previously unreported missense mutation in the KRT25 gene causing ARH with woolly hair.
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics," Moscow, Russia. Electronic address: nzernov01@gmail.com.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Zernov
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics," Moscow, Russia; The Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia.
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Skoblov
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics," Moscow, Russia; Regenerative and Genetic Medical Center of the Human Stem Cells Institute, Moscow, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Marakhonov
authors.affiliation: Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics," Moscow, Russia.
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Vasilyeva
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics," Moscow, Russia; Regenerative and Genetic Medical Center of the Human Stem Cells Institute, Moscow, Russia.
authors.forename: Fedor A
authors.initials: FA
authors.lastname: Konovalov
authors.affiliation: Ministry of Health and Social Development of Chuvash Republic, Presidential Perinatal Center, Chuvash Republic, Cheboksary, Russia.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Abrukova
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics," Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia; Moscow State University of Medicine and Dentistry, Moscow, Russia.
authors.forename: Rena A
authors.initials: RA
authors.lastname: Zinchenko
mesh_terms: D000505:Alopecia / Q000151:congenital* / Q000208:ethnology / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006197:Hair / Q000002:abnormalities; D006201:Hair Diseases; D018859:Hair Follicle / Q000473:pathology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D053564:Keratins, Hair-Specific / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012426:Russia; D012494:Sampling Studies; D017384:Sequence Deletion
chemical_list: D053564:Keratins, Hair-Specific