A Novel Homozygous Variant in the DSP Gene Underlies the First Case of Non-Syndromic Form of Alopecia

In 2015, researchers discovered a novel homozygous variant in the DSP gene, which was associated with non-syndromic alopecia in a consanguineous Pakistani family. The mutation [c.1493C > T (p.Pro498Leu)] affects the SH3 domain of desmoplakin, a key protein for cell structural integrity, particularly in the epidermis. Although DSP gene mutations have been linked to heart issues, the affected individuals in this study did not exhibit any cardiac abnormalities. The study highlights the genetic diversity of hereditary hair loss disorders and suggests that this form of alopecia may be related to cardiocutaneous syndromes. The variant was rare, with a very low allele frequency in the Exome Aggregation Consortium database, and was not previously reported in a homozygous state. The findings underscore the importance of the DSP gene in hair development and alopecia pathogenesis, and call for further research to understand how DSP mutations affect desmosome stability and function. The exact number of participants in the study was not mentioned.