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 Zhang, Xin A1 Guo, Bi-Rong A1 Cai, Li-Qiong A1 Jiang, Tao A1 Sun, Liang-Dan A1 Cui, Yong A1 Hu, Jing-Chu A1 Zhu, Jun A1 Chen, Gang A1 Tang, Xian-Fa A1 Sun, Guang-Qing A1 Tang, Hua-Yang A1 Liu, Yuan A1 Li, Min A1 Li, Qi-Bin A1 Cheng, Hui A1 Gao, Min A1 Li, Ping A1 Yang, Xu A1 Zuo, Xian-Bo A1 Zheng, Xiao-Dong A1 Wang, Pei-Guang A1 Wang, Jian A1 Wang, Jun A1 Liu, Jian-Jun A1 Yang, Sen A1 Li, Ying-Rui A1 Zhang, Xue-Jun 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 This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group.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.