Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency

DSpace/Manakin Repository

Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency

Citable link to this page

 

 
Title: Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency
Author: Lieber, Daniel S; Hershman, Steven G; Slate, Nancy G; Calvo, Sarah E; Sims, Katherine B; Schmahmann, Jeremy D; Mootha, Vamsi K

Note: Order does not necessarily reflect citation order of authors.

Citation: Lieber, Daniel S, Steven G Hershman, Nancy G Slate, Sarah E Calvo, Katherine B Sims, Jeremy D Schmahmann, and Vamsi K Mootha. 2014. “Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency.” BMC Medical Genetics 15 (1): 30. doi:10.1186/1471-2350-15-30. http://dx.doi.org/10.1186/1471-2350-15-30.
Full Text & Related Files:
Abstract: Background: D-bifunctional protein deficiency, caused by recessive mutations in HSD17B4, is a severe, infantile-onset disorder of peroxisomal fatty acid oxidation. Few affected patients survive past two years of age. Compound heterozygous mutations in HSD17B4 have also been reported in two sisters diagnosed with Perrault syndrome (MIM # 233400), who presented in adolescence with ovarian dysgenesis, hearing loss, and ataxia. Case presentation: An adult male presented with cerebellar ataxia, peripheral neuropathy, hearing loss, and azoospermia. The clinical presentation, in combination with biochemical findings in serum, urine, and muscle biopsy, suggested a mitochondrial disorder. Commercial genetic testing of 18 ataxia and mitochondrial disease genes was negative. Targeted exome sequencing followed by analysis of single nucleotide variants and small insertions/deletions failed to reveal a genetic basis of disease. Application of a computational algorithm to infer copy number variants (CNVs) from exome data revealed a heterozygous 12 kb deletion of exons 10–13 of HSD17B4 that was compounded with a rare missense variant (p.A196V) at a highly conserved residue. Retrospective review of patient records revealed mildly elevated ratios of pristanic:phytanic acid and arachidonic:docosahexaenoic acid, consistent with dysfunctional peroxisomal fatty acid oxidation. Conclusion: Our case expands the phenotypic spectrum of HSD17B4-deficiency, representing the first male case reported with infertility. Furthermore, it points to crosstalk between mitochondria and peroxisomes in HSD17B4-deficiency and Perrault syndrome.
Published Version: doi:10.1186/1471-2350-15-30
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015298/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406923
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters