These authors contributed equally to this work.
Novel homozygous mutation in DSP causing skin fragility–woolly hair syndrome: report of a large family and review of the desmoplakin-related phenotypes
Version of Record online: 22 JUL 2010
© 2010 John Wiley & Sons A/S
Volume 80, Issue 1, pages 50–58, July 2011
How to Cite
Al-Owain, M., Wakil, S., Shareef, F., Al-Fatani, A., Hamadah, E., Haider, M., Al-Hindi, H., Awaji, A., Khalifa, O., Baz, B., Ramadhan, R. and Meyer, B. (2011), Novel homozygous mutation in DSP causing skin fragility–woolly hair syndrome: report of a large family and review of the desmoplakin-related phenotypes. Clinical Genetics, 80: 50–58. doi: 10.1111/j.1399-0004.2010.01518.x
- Issue online: 8 JUN 2011
- Version of Record online: 22 JUL 2010
- Accepted manuscript online: 22 JUL 2010 12:00AM EST
- Received 17 May 2010, revised and accepted for publication 19 July 2010
- linkage analysis;
- palmoplantar keratoderma;
- skin fragility;
- woolly hair syndrome
Al-Owain M, Wakil S, Shareef F, Al-Fatani A, Hamadah E, Haider M, Al-Hindi H, Awaji A, Khalifa O, Baz B, Ramadhan R, Meyer B. Novel homozygous mutation in DSP causing skin fragility–woolly hair syndrome: report of a large family and review of the desmoplakin-related phenotypes.
Desmoplakin is an important cytoskeletal linker for the function of the desmosomes. Linking desmoplakin to certain types of cardiocutaneous syndromes has been a hot topic recently. Skin fragility–woolly hair syndrome is a rare autosomal recessive disorder involving the desmosomes and is caused by mutation in the desmoplakin gene (DSP). We report five members from a large family with skin fragility–woolly hair syndrome. The index is a 14-year-old girl with palmoplantar keratoderma, woolly hair, variable alopecia, dystrophic nails, and excessive blistering to trivial mechanical trauma. No cardiac symptoms were reported. Although formal cardiac examination was not feasible, the echocardiographic evaluation of the other two affected younger siblings was normal. Homozygosity mapping and linkage analysis revealed a high LOD score region in the short arm of chromosome 6 that harbors the DSP. Full sequencing of the DSP showed a novel homozygous c.7097 G>A (p.R2366H) mutation in all affected members, and the parents were heterozygous. This is the report of the third case/family of the skin fragility–woolly hair syndrome in the literature. We also present a clinical and molecular review of various desmoplakin-related phenotypes, with emphasis on onset of cardiomyopathy. The complexity of the desmoplakin and its variable presentations warrant introducing the term ‘desmoplakinopathies’ to describe all the phenotypes related to defects in the desmoplakin.