Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency

Amor, D.J., Marsh, A.P.L., Storey, E., Tankard, R.ORCID: 0000-0002-8847-9401, Gillies, G., Delatycki, M.B., Pope, K., Bromhead, C., Leventer, R.J., Bahlo, M. and Lockhart, P.J. (2016) Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency. Neurology Genetics, 2 (6). e114.

Abstract

Objective: To determine the genetic cause of slowly progressive cerebellar ataxia, sensorineural deafness, and hypergonadotropic hypogonadism in 5 patients from 3 different families.

Methods: The patients comprised 2 sib pairs and 1 sporadic patient. Clinical assessment included history, physical examination, and brain MRI. Linkage analysis was performed separately on the 2 sets of sib pairs using single nucleotide polymorphism microarrays, followed by analysis of the intersection of the regions. Exome sequencing was performed on 1 affected patient with variant filtering and prioritization undertaken using these intersected regions.

Results: Using a combination of sequencing technologies, we identified compound heterozygous mutations in HSD17B4 in all 5 affected patients. In all 3 families, peroxisomal D-bifunctional protein (DBP) deficiency was caused by compound heterozygosity for 1 nonsense/deletion mutation and 1 missense mutation.

Conclusions: We describe 5 patients with juvenile DBP deficiency from 3 different families, bringing the total number of reported patients to 14, from 8 families. This report broadens and consolidates the phenotype associated with juvenile DBP deficiency.

Item Type:	Journal Article
Publisher:	Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Copyright:	© 2016 American Academy of Neurology
URI:	http://researchrepository.murdoch.edu.au/id/eprint/52052

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