RT Journal Article SR Electronic T1 Exome sequencing identified a missense mutation of EPS8L3 in Marie Unna hereditary hypotrichosis JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 727 OP 730 DO 10.1136/jmedgenet-2012-101134 VO 49 IS 12 A1 Xin Zhang A1 Bi-Rong Guo A1 Li-Qiong Cai A1 Tao Jiang A1 Liang-Dan Sun A1 Yong Cui A1 Jing-Chu Hu A1 Jun Zhu A1 Gang Chen A1 Xian-Fa Tang A1 Guang-Qing Sun A1 Hua-Yang Tang A1 Yuan Liu A1 Min Li A1 Qi-Bin Li A1 Hui Cheng A1 Min Gao A1 Ping Li A1 Xu Yang A1 Xian-Bo Zuo A1 Xiao-Dong Zheng A1 Pei-Guang Wang A1 Jian Wang A1 Jun Wang A1 Jian-Jun Liu A1 Sen Yang A1 Ying-Rui Li A1 Xue-Jun Zhang YR 2012 UL http://jmg.bmj.com/content/49/12/727.abstract AB 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 This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group.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.