Peroxisomal D-bifunctional protein deficiency: three adults diagnosed by whole-exome sequencing.

ABSTRACT:

Objective

To determine the causative genetic lesion in 3 adult siblings with a slowly progressive, juvenile-onset phenotype comprising cerebellar atrophy and ataxia, intellectual decline, hearing loss, hypogonadism, hyperreflexia, a demyelinating sensorimotor neuropathy, and (in 2 of 3 probands) supratentorial white matter changes, in whom numerous prior investigations were nondiagnostic.

Methods

The patients' initial clinical assessment included history and physical examination, cranial MRI, and nerve conduction studies. We performed whole-exome sequencing of all 3 probands, followed by variant annotation and selection of rare, shared, recessive coding changes to identify the gene responsible. We next performed a panel of peroxisomal investigations in blood and cultured fib

SUBMITTER: Lines MA 

PROVIDER: S-EPMC3963001 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature