Hair Loss

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Monday, August 3, 2009

A Gene for Hair Loss
J Dermatol Sci. 2008 Apr;50(1):25-30.

Mutations in the hairless gene underlie APL in three families of Pakistani origin.

Kraemer L, Wajid M, Shimomura Y, Christiano AM.

BACKGROUND: Atrichia with papular lesions (APL) (OMIM#209500) is a rare autosomal recessively inherited form of irreversible alopecia characterized by papular lesions of keratin-filled cysts on various regions of the body. Males and females are equally affected and present with a distinct pattern of total hair loss on scalp, axilla and body. It begins shortly after birth with the development of hair loss, and patients are normally devoid of eyelashes and eyebrows. Mutations in the hairless (HR) gene have been previously shown to be responsible for APL.

OBJECTIVE: In this study, we studied the molecular basis of APL in three unrelated families of Pakistani origin. METHOD: Molecular analysis of the HR genes was performed on genomic DNA from probands and family members. RESULTS: DNA sequencing of the HR gene in family A revealed a novel homozygous 2bp deletion in exon 6 leading to a frameshift and a downstream premature termination codon in
exon 8 (1782-83delAG). In family B, we identified a novel homozygous deletion of a G nucleotide at the exon 15-intron 15 boundary, termed 3097delG. Family C carries a previously reported missense mutation consisting of an A-to-G transition at nucleotide 276 resulting in the mutation N970S in exon 14.
CONCLUSION: Two mutations identified in this study are novel mutations in the HR gene and extend the body of evidence implicating the hairless gene family in the pathogenesis of human skin disorders. The one previously reported mutation suggests it may represent a recurrent mutation, or alternatively, an allele that is widely dispersed around the world.

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Genetics of Male Pattern Hair Loss
Am J Hum Genet. 2008 Mar;82(3):737-43.
Hillmer AM, et al,  Genome-wide scan and fine-mapping linkage study of androgenetic alopecia reveals a locus on chromosome 3q26.

Androgenetic alopecia (AGA, male pattern baldness) is the most common form of hair loss. The origin of AGA is genetic, with the X chromosome located androgen receptor gene (AR) being the only risk gene identified to date. We present the results of a genome-wide linkage study of 95 families and linkage fine mapping of the 3q21-q29, 11q14-q25, 18p11-q23, and 19p13-q13 regions in an extended sample
of 125 families of German descent. The locus with strongest evidence for linkage  was mapped to 3q26with a nonparametric linkage (NPL) score of 3.97 (empirical p value = 0.00055). This is the first step toward the identification of new susceptibility genes in AGA, a process which will provide important insights into the molecular and cellular basis of scalp hair loss.

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