Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency
- Author(s)
- Amor, DJ; Marsh, AP; Storey, E; Tankard, R; Gillies, G; Delatycki, MB; Pope, K; Bromhead, C; Leventer, RJ; Bahlo, M; Lockhart, PJ;
- Details
- Publication Year 2016-12,Volume 2,Issue #6,Page e114
- Journal Title
- Neurol Genet
- Publication Type
- Journal Article
- 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.
- Publisher
- American Academy of Neurology
- Research Division(s)
- Population Health And Immunity
- Publisher's Version
- https://doi.org/10.1212/NXG.0000000000000114
- Open Access at Publisher's Site
http://ng.neurology.org/content/2/6/e114.full- ARC Grants
- ARC/FT100100764,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-11-01 12:04:12
Last Modified: 2016-11-01 12:14:18