TY - JOUR T1 - Exome sequencing identified a missense mutation of <em>EPS8L3</em> in Marie Unna hereditary hypotrichosis JF - Journal of Medical Genetics JO - J Med Genet SP - 727 LP - 730 DO - 10.1136/jmedgenet-2012-101134 VL - 49 IS - 12 AU - Xin Zhang AU - Bi-Rong Guo AU - Li-Qiong Cai AU - Tao Jiang AU - Liang-Dan Sun AU - Yong Cui AU - Jing-Chu Hu AU - Jun Zhu AU - Gang Chen AU - Xian-Fa Tang AU - Guang-Qing Sun AU - Hua-Yang Tang AU - Yuan Liu AU - Min Li AU - Qi-Bin Li AU - Hui Cheng AU - Min Gao AU - Ping Li AU - Xu Yang AU - Xian-Bo Zuo AU - Xiao-Dong Zheng AU - Pei-Guang Wang AU - Jian Wang AU - Jun Wang AU - Jian-Jun Liu AU - Sen Yang AU - Ying-Rui Li AU - Xue-Jun Zhang Y1 - 2012/12/01 UR - http://jmg.bmj.com/content/49/12/727.abstract N2 - 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-&gt;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 This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group.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. ER -