Exome sequencing released a case of X-linked adrenoleukodystrophy mimicking recessive hereditary spastic paraplegia.

[x-linked adrenoleukodystrophy]

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 .1661 G >A , p .R 554 H ) was identified in ABCD 1 . Subsequently , PCR-based direct sequencing of other family members revealed that the mutation was co -segregating with the disease , indicating that ABCD 1 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 .