We describe a new autosomal recessive white matter disorder ('hypomyelination and congenital cataract') characterized by hypomyelination of the central and peripheral nervous system, progressive neurological impairment and congenital cataract. We identified mutations in five affected families, resulting in a deficiency of hyccin, a newly identified 521–amino acid membrane protein. Our study highlights the essential role of hyccin in central and peripheral myelination.
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We thank R. Gatti, P. Palazzolo, V. Costa and the families of the affected individuals for their collaborative efforts and P. Broda for technical assistance. This work has been supported by the Pierfranco and Luisa Mariani Foundation ONLUS (grant R-04-37), the Telethon Italy Foundation (grant GGP05156), the Istituto Superiore della Sanità (grant 526/A32) and a donation from R. Bulgarelli. F.S. and M.P.L. were supported by grants from the US National Institutes of Health and the American Heart Association. The samples were obtained from the 'Cell Line and DNA Bank from Patients Affected by Genetic Diseases' collection (http://www.gaslini.org/labdppm.htm) supported by Italian Telethon grants (project number GTF04002).
The authors declare no competing financial interests.
Pedigrees and chromosome 7p21.1-p15.3 haplotypes in five HCC families. (PDF 153 kb)
Multiple sequence alignment of hyccin. (PDF 386 kb)
Expression analysis of DRCTNNB1A. (PDF 286 kb)
Prediction of membrane-spanning regions of hyccin by TMpred. (PDF 61 kb)
Immunoblot analysis of transfected COS-7 cells. (PDF 114 kb)
Clinical and neurological findings. (PDF 68 kb)
Family-specific and cumulative lod scores for chromosome 7 markers. (PDF 60 kb)
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Zara, F., Biancheri, R., Bruno, C. et al. Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract. Nat Genet 38, 1111–1113 (2006). https://doi.org/10.1038/ng1870
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