title: Exome sequencing identified a missense mutation of EPS8L3 in Marie Unna hereditary hypotrichosis.
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 This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group.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.
authors.affiliation: Department of Dermatology, Institute of Dermatology, No. 1 Hospital, Anhui Medical University, 69 Meishan Road, Hefei, Anhui 230032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Bi-Rong
authors.initials: BR
authors.lastname: Guo
authors.forename: Li-Qiong
authors.initials: LQ
authors.lastname: Cai
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Liang-Dan
authors.initials: LD
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Jing-Chu
authors.initials: JC
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xian-Fa
authors.initials: XF
authors.lastname: Tang
authors.forename: Guang-Qing
authors.initials: GQ
authors.lastname: Sun
authors.forename: Hua-Yang
authors.initials: HY
authors.lastname: Tang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Qi-Bin
authors.initials: QB
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zheng
authors.forename: Pei-Guang
authors.initials: PG
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Ying-Rui
authors.initials: YR
authors.lastname: Li
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D005838:Genotype; D006801:Humans; D007039:Hypotrichosis / Q000151:congenital* / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C581607:EPS8L3 protein, human