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Mitochondrial Mutations Make Malformed Manes

In Björnstad syndrome, mutations in the BCS1L gene lead to abnormal hair formation.

Björnstad syndrome is characterized by congenital sensorineural deafness and pili torti (flattened, twisted hair shafts) that becomes obvious during the first 2 years of life. The discovery that this syndrome is related to abnormal mitochondrial metabolism demonstrates the importance of mitochondria in skin biology and disease.

Researchers used refined genetic mapping and DNA sequencing in unrelated families to identify BCS1L at chromosome 2q34–36 as the gene responsible for Björnstad syndrome. BCS1L is an ATPase, a chaperone protein that mediates protein folding and interactions and is necessary for complex III formation in mitochondria. Mutations in BCS1L have two important effects: reduction of mitochondrial electron transport and increased production of reactive oxygen species. Reactive oxygen species (e.g., superoxides) are known to be destructive to many types of cells.

The key finding in the current research was that although all BCS1L mutations increased the production of reactive oxygen species, the amount of increase was specific to the mutation and the clinical disease. In Björnstad syndrome, electron transport was decreased by 38%, but the production of reactive oxygen species increased 30-fold!

Comment: Mitochondria are an important subject of study during the first year of medical school; they are currently making a comeback in clinical relevance. Genetic diseases of the mitochondria may be caused by maternally inherited mitochondrial genes or by nuclear Mendelian genes that affect mitochondrial function. BCS1L is a typical Mendelian gene. Mitochondria have an essential role in apoptosis through the release of cytochrome c. This report establishes the importance of mitochondria in general, and reactive oxygen intermediates in particular, in hair metabolism and disease: Patients with Menkes disease have pili torti, altered cytochrome c oxidase activity, and decreased mitochondrial function. Cartilage hair hypoplasia is linked to a defect in mitochondrial RNA cleavage. The mitochondrial clues and footprints in such other diseases as acquired pili torti, androgenetic alopecia, and alopecia areata await investigation.

— Lowell A. Goldsmith, MD

Published in Journal Watch Dermatology February 21, 2007

Citation(s):

Hinson JT et al. Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome. N Engl J Med 2007 Feb 22; 356:809-19.

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