2. Academic Validation
  3. Exome sequencing identified a missense mutation of EPS8L3 in Marie Unna hereditary hypotrichosis

Exome sequencing identified a missense mutation of EPS8L3 in Marie Unna hereditary hypotrichosis

  • J Med Genet. 2012 Dec;49(12):727-30. doi: 10.1136/jmedgenet-2012-101134.
Xin Zhang 1,  Bi-Rong Guo,  Li-Qiong Cai,  Tao Jiang,  Liang-Dan Sun,  Yong Cui,  Jing-Chu Hu,  Jun Zhu,  Gang Chen,  Xian-Fa Tang,  Guang-Qing Sun,  Hua-Yang Tang,  Yuan Liu,  Min Li,  Qi-Bin Li,  Hui Cheng,  Min Gao,  Ping Li,  Xu Yang,  Xian-Bo Zuo,  Xiao-Dong Zheng,  Pei-Guang Wang,  Jian Wang,  Jun Wang,  Jian-Jun Liu,  Sen Yang,  Ying-Rui Li,  Xue-Jun Zhang
Affiliations

Affiliation

  • 1 Department of Dermatology, Institute of Dermatology, No. 1 Hospital, Anhui Medical University, 69 Meishan Road, Hefei, Anhui 230032, China.
PMID: 23099647 DOI: 10.1136/jmedgenet-2012-101134
Abstract

Background: Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant disorder characterised by coarse, wiry, twisted hair developed in early childhood and subsequent progressive hair loss. MUHH is a genetically heterogeneous disorder. No gene in 1p21.1-1q21.3 region responsible for MUHH has been identified.

Methods: Exome Sequencing was performed on two affected subjects, who had normal vertex hair and modest alopecia, and one unaffected individual from a four-generation MUHH family of which our previous linkage study mapped the MUHH locus on chromosome 1p21.1-1q21.3.

Results: We identified a missense mutation in EPS8L3 (NM_024526.3: exon2: c.22G->A:p.Ala8Thr) within 1p21.1-1q21.3. Sanger Sequencing confirmed the cosegregation of this mutation with the disease phenotype in the family by demonstrating the presence of the heterozygous mutation in all the eight affected and absence in all the seven unaffected individuals. This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of Other disease from another unpublished project of our group.

Conclusions: Taken together, our results suggest that EPS8L3 is a causative gene for MUHH, which was helpful for advancing us on understanding of the pathogenesis of MUHH. Our study also has further demonstrated the effectiveness of combining exome Sequencing with linkage information for identifying Mendelian disease genes.

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