title: Exome sequencing released a case of X-linked adrenoleukodystrophy mimicking recessive hereditary spastic paraplegia.
abstract: Genetic heterogeneity is common in many Mendelian disorders such as hereditary spastic paraplegia (HSP), which makes the genetic diagnosis more complicated. The goal of this study was to investigate a Chinese family with recessive hereditary spastic paraplegia, of which causative mutations could not be identified using the conventional PCR-based direct sequencing. Next-generation sequencing of all the transcripts of whole genome exome, after on-array hybrid capture, was performed on two affected male subjects (the proband and his brother). A missense mutation (c.1661G>A, p.R554H) was identified in ABCD1. Subsequently, PCR-based direct sequencing of other family members revealed that the mutation was co-segregating with the disease, indicating that ABCD1 mutation was the pathogenic event for this family. Very long-chain fatty acids (VLCFA) assay in the two affected cases confirmed X-ALD. Our study suggests exome sequencing can be used not only to find a novel causative gene, but also to quickly identify mutations of known genes when the clinical elements are etiologically misleading.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Zi-Xiong
authors.initials: ZX
authors.lastname: Zhan
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Liao
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Luo
authors.forename: Zhao-Ting
authors.initials: ZT
authors.lastname: Hu
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Wang
authors.forename: Xin-Xiang
authors.initials: XX
authors.lastname: Yan
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.forename: Mei-Zhi
authors.initials: MZ
authors.lastname: Dai
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Bei-Sha
authors.initials: BS
authors.lastname: Tang
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000326:Adrenoleukodystrophy / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D003937:Diagnosis, Differential; D059472:Exome / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters
keywords: ABCD1 gene; Genetic heterogeneity; Hereditary spastic paraplegia; Whole-exome sequencing