ORPHA: 170; DO: 0111573;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q13.13 | Woolly hair, autosomal dominant | 194300 | Autosomal dominant | 3 | KRT74 | 608248 |
A number sign (#) is used with this entry because of evidence that autosomal dominant woolly hair (ADWH) is caused by heterozygous mutation in the KRT74 gene (608248) on chromosome 12q13.
Woolly hair (WH) refers to a group of hair shaft disorders that are characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, WH grows slowly and stops growing after a few inches. Under light microscopy, WH shows some structural anomalies, including trichorrhexis nodosa and tapered ends. WH can appear as part of several syndromes, such as Naxos disease (601214) and cardiofaciocutaneous syndrome (115150) (summary by Petukhova et al., 2009).
See 278150 for a discussion of genetic heterogeneity of autosomal recessive woolly hair.
Mohr (1932) reported a Norwegian kindred in which many members had hair that was short, tightly curled, and woolly, resembling the hair of black persons. Mohr (1932) considered black admixture very unlikely in this family. Gossage (1907) reported a family. Anderson (1936) and Schokking (1934) also reported Caucasian families with many affected. Anderson (1936), who had close familiarity with the hair of blacks, felt that the woolly hair was different.
Hutchinson et al. (1974) distinguished dominant and recessive forms. In the autosomal dominant trait, a variable degree of tight curling is present in all hairs throughout the scalp. In the autosomal recessive form, abnormal, tightly-curled, fine, white or blond hair tends to be short and is present from birth. A third type of woolly hair is the woolly hair nevus, in which the hair within a well-demarcated area is lighter than the normal hair and has a reduced diameter.
Mortimer (1985) discussed differential diagnosis of unruly hair.
Ormerod et al. (1987) described a family in which 6 members of 3 sibships and 2 generations, and presumably a seventh person in an earlier generation, showed an unusual form of woolly hair: normal and woolly hairs were intimately interspersed throughout the scalp. Twenty to 38% of the hairs were abnormal in the several family members.
Taylor (1990) described a family with 10 affected individuals in 4 generations with an instance of male-to-male transmission. The proposita had Coats disease of the eye (see 194300), which was, however, present in no other family members.
Shimomura et al. (2010) reported a 4-generation Pakistani family with woolly hair segregating as an autosomal dominant trait. Multiple affected family members displayed the clinical features at birth, with hair over the entire scalp region being coarse, lusterless, dry, and tightly curled, leading to a diffuse woolly hair phenotype with normal hair density. The hair grew slowly and stopped growing at a few inches. Under light microscopy, plucked hairs from affected individuals showed dystrophic anagen hairs, twisting, knot formation, and tapered distal ends. Eyebrows, eyelashes, and beard hairs appeared normal, and affected individuals had normal teeth, nails, and sweating, without palmoplantar hyperkeratosis (see 144200) or keratosis pilaris (604093).
Wasif et al. (2011) described a 4-generation consanguineous Pakistani family segregating autosomal dominant woolly hair. The hair was 2 to 3 inches long, tightly curled, twisted, and entangled. There were 10 affected individuals in the family, 9 of whom were alive.
The transmission pattern of ADWH in the family reported by Shimomura et al. (2010) was consistent with autosomal dominant inheritance.
In a Pakistani family segregating autosomal dominant woolly hair, Shimomura et al. (2010) performed whole-genome linkage analysis and found suggestive linkage on chromosome 12. Haplotype and microsatellite analyses defined a 20.91-Mb linkage interval flanked by markers D12S1301 and D12S1610 on chromosome 12q13.
In affected individuals of a Pakistani family segregating autosomal dominant woolly hair mapping to chromosome 12q13, Shimomura et al. (2010) identified heterozygosity for a missense mutation (608248.0001) in the KRT74 gene.
In 9 affected members of a consanguineous Pakistani family segregating autosomal dominant woolly hair, Wasif et al. (2011) identified a splice acceptor site mutation in the KRT74 gene (608248.0002). The mutation was not found in 7 unaffected family members or in 100 ethnically matched, unrelated control individuals.
Anderson, E. An American pedigree for woolly hair. J. Hered. 27: 444 only, 1936.
Gossage, A. M. The inheritance of certain human abnormalities. Quart. J. Med. 1: 331-347, 1907.
Hutchinson, P. E., Cairns, R. J., Wells, R. S. Woolly hair: clinical and general aspects. Trans. St. Johns Hosp. Derm. Soc. 60: 160-177, 1974. [PubMed: 4467886]
Mohr, O. L. Woolly hair, a dominant mutant character in man. J. Hered. 23: 345-352, 1932.
Mortimer, P. S. Unruly hair. Brit. J. Derm. 113: 467-473, 1985. [PubMed: 4063181] [Full Text: https://doi.org/10.1111/j.1365-2133.1985.tb02362.x]
Ormerod, A. D., Main, R. A., Ryder, M. L., Gregory, D. W. A family with diffuse partial woolly hair. Brit. J. Derm. 116: 401-405, 1987. [PubMed: 3567076] [Full Text: https://doi.org/10.1111/j.1365-2133.1987.tb05855.x]
Petukhova, L., Shimomura, Y., Wajid, M., Gorroochurn, P., Hodge, S. E., Christiano, A. M. The effect of inbreeding on the distribution of compound heterozygotes: a lesson from lipase H mutations in autosomal recessive woolly hair/hypotrichosis. Hum. Hered. 68: 117-130, 2009. [PubMed: 19365138] [Full Text: https://doi.org/10.1159/000212504]
Sanders, J. Eine Familie mit Kraushaar. Genetica 18: 97-104, 1936.
Schokking, C. P. Another woolly hair mutation in man. J. Hered. 25: 337-340, 1934.
Shimomura, Y., Wajid, M., Petukhova, L., Kurban, M., Christiano, A. M. Autosomal-dominant woolly hair resulting from disruption of keratin 74 (KRT74), a potential determinant of human hair texture. Am. J. Hum. Genet. 86: 632-638, 2010. [PubMed: 20346438] [Full Text: https://doi.org/10.1016/j.ajhg.2010.02.025]
Taylor, A. E. M. Hereditary woolly hair with ocular involvement. Brit. J. Derm. 123: 523-525, 1990. [PubMed: 2095184] [Full Text: https://doi.org/10.1111/j.1365-2133.1990.tb01459.x]
Verbov, J. Woolly hair--study of a family. Dermatologica 157: 42-47, 1978. [PubMed: 668970] [Full Text: https://doi.org/10.1159/000250807]
Wasif, N., Naqvi, S. K. u.-H., Basit, S., Ali, N., Ansar, M., Ahmad, W. Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families. Hum. Genet. 129: 419-424, 2011. [PubMed: 21188418] [Full Text: https://doi.org/10.1007/s00439-010-0938-9]