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

Title: Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency
Authors: Amor, DJ; Marsh, APL; Storey, E; Tankard, R; Gillies, G; Delatycki, MB; Pope, K; Bromhead, C; Leventer, RJ; Bahlo, M; Lockhart, PJ
Publisher Information: LIPPINCOTT WILLIAMS & WILKINS
Publication Year: 2016
Collection: The University of Melbourne: Digital Repository
Description: 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.
Document Type: article in journal/newspaper
Language: English
ISSN: 2376-7839
Relation: NHMRC/APP1032364; pii: NG2016003277; https://hdl.handle.net/11343/219699
Availability: https://hdl.handle.net/11343/219699
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND
Accession Number: edsbas.829B1E2C
Database: BASE