Uniparental disomy of chromosome 16 unmasks recessive mutations of FA2H/SPG35 in 4 families.

ABSTRACT:

Objective

Identifying an intriguing mechanism for unmasking recessive hereditary spastic paraplegias.

Method

Herein, we describe 4 novel homozygous FA2H mutations in 4 nonconsanguineous families detected by whole-exome sequencing or a targeted gene panel analysis providing high coverage of all known hereditary spastic paraplegia genes.

Results

Segregation analysis revealed in all cases only one parent as a heterozygous mutation carrier whereas the other parent did not carry FA2H mutations. A macro deletion within FA2H, which could have caused a hemizygous genotype, was excluded by multiplex ligation-dependent probe amplification in all cases. Finally, a microsatellite array revealed uniparental disomy (UPD) in all 4 families leading to homozygous FA2H mutations. UPD w

SUBMITTER: Soehn AS 

PROVIDER: S-EPMC4940069 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature