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

David J Amor, Ashley P L Marsh, Elsdon Storey, Rick Tankard, Greta Gillies, Martin Delatycki, Kate Pope, Catherine J Bromhead, Richard Jacob Leventer, Melanie Bahlo, Paul J Lockhart

Research output: Contribution to journalArticleResearchpeer-review


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.
Original languageEnglish
Article numbere114
Number of pages8
Issue number6
Publication statusPublished - Dec 2016


  • coenzyme
  • D-bifunctional protein
  • follicle-stimulating hormone
  • luteinizing hormone
  • massively parallel sequencing
  • single nucleotide polymorphism
  • very long-chain fatty acid

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