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Case Reports
. 2015 Oct;52(10):676-80.
doi: 10.1136/jmedgenet-2015-103255. Epub 2015 Jul 9.

A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair

Muhammad Ansar  1 , Syed Irfan Raza  2 , Kwanghyuk Lee  3 , Irfanullah  4 , Shamim Shahi  4 , Anushree Acharya  3 , Hang Dai  3 , Joshua D Smith  5 , Jay Shendure  5 , Michael J Bamshad  5 , Deborah A Nickerson  5 , Regie Lyn P Santos-Cortez  3 , Wasim Ahmad  4 , Suzanne M Leal  3
Affiliations
Case Reports

A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair

Muhammad Ansar et al. J Med Genet. 2015 Oct.

Abstract

Background: Woolly hair (WH) is a hair abnormality that is primarily characterised by tightly curled hair with abnormal growth.

Methods: In two unrelated consanguineous Pakistani families with non-syndromic autosomal recessive (AR) WH, homozygosity mapping and linkage analysis identified a locus within 17q21.1-q22, which contains the type I keratin gene cluster. A DNA sample from an affected individual from each family underwent exome sequencing.

Results: A homozygous missense variant c.950T>C (p.(Leu317Pro)) within KRT25 segregated with ARWH in both families, and has a combined maximum two-point LOD score of 7.9 at ϴ=0. The KRT25 variant is predicted to result in disruption of the second α-helical rod domain and the entire protein structure, thus possibly interfering with heterodimerisation of K25 with type II keratins within the inner root sheath (IRS) of the hair follicle and the medulla of the hair shaft.

Conclusions: Our findings implicate a novel gene involved in human hair abnormality, and are consistent with the curled, fragile hair found in mice with Krt25 mutations, and further support the role of IRS-specific type I keratins in hair follicle development and maintenance of hair texture.

Keywords: K25; KRT25; autosomal recessive woolly hair; inner root sheath; type I keratin gene cluster.

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Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
Pedigree drawings, haplotypes and sparse, woolly hair in families AP188 and AP216. (A and B) Drawings of pedigrees AP188 and AP216 displaying segregation of the identical SNP haplotype (within rectangles) and the KRT25 c.950T>C variant with autosomal recessive woolly hair. Arrows indicate affected individuals whose DNA samples were submitted for exome sequencing. (C) Individual VI-4 from AP188 had woolly hair at age 8 years. (D and E) Individual VI-5 from AP188 had sparse, soft hairs on scalp at age 1 year. (F and H) Individual II-4 from AP216 with woolly hair at age 8 years. (G) Sparse, woolly hair is more obvious in 10-year-old female II-2 from AP216 who has long hair.
See this image and copyright information in PMC

References

    1. McLean WHI, Moore CBT. Keratin disorders: from gene to therapy. Hum Mol Genet. 2011;20:R189–97. - PubMed
    1. Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev. 2001;81:449–94. - PubMed
    1. Langbein L, Rogers MA, Praetzel-Wunder S, Helmke B, Schirmacher P, Schweizer J. K25 (K25irs1), K26 (K25irs2), K27 (K25irs3), and K28 (K25irs4) represent the type I inner root sheath keratins of the human hair follicle. J Invest Dermatol. 2006;26:2377–86. - PubMed
    1. Harel S, Christiano AM. Genetics of structural hair disorders. J Invest Dermatol. 2012;132:E22–6. - PubMed
    1. Shimomura Y, Garzon MC, Kristal L, Shapiro L, Christiano AM. Autosomal recessive woolly hair with hypotrichosis caused by a novel homozygous mutation in the P2RY5 gene. Exp Dermatol. 2009;18:218–21. - PMC - PubMed

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