Evidence map›Paper›PMID 24602372›Full record

ArticleBMC medical genetics2014

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

Daniel S Lieber, Steven G Hershman, Nancy G Slate, Sarah E Calvo, Katherine B Sims, Jeremy D Schmahmann, Vamsi K Mootha

Open access · goldAbstract readCase Reports
In one paragraph

Article in BMC medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Neurology. Genetics · 2026
    Article
  3. Article
  4. A Homozygous Missense Variant inMolecular syndromology · 2024
    Article
  5. Article
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  8. Article
  9. Biallelic mutation ofNeurology. Genetics · 2020
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. A Novel Mechanism to Drive Castration-Resistant Prostate Cancer.Trends in endocrinology and metabolism: TEM · 2018
    Article
  16. Article
  17. Review
  18. Heterozygous mutations inNeurology. Genetics · 2016
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 1 country.

Daniel S Lieber
Steven G Hershman
Nancy G Slate
Sarah E Calvo
Katherine B Sims
Jeremy D SchmahmannAtaxia Unit, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Massachusetts General Hospital & Harvard Medical School, Boston, MA 02114 USA, jschmahmann@partners.org
Vamsi K Mootha
Harvard University · USMassachusetts General Hospital · USCenter for Human Genetics · USCenter for Systems Biology · USHoward Hughes Medical Institute · US

Funding

Defining the genetic basis of human respiratory chain diseaseRC2HG005556 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI MOOTHA, VAMSI KRISHNA · 2009 to 2010
$2.3M
Human Mitochondrial Disease: From Novel Gene Variants to Causality and FunctionR01GM097136 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI MOOTHA, VAMSI KRISHNA · 2011 to 2014
$2.0M
NHGRI NIH HHS RC2HG005556NIGMS NIH HHS R01 GM097136NIGMS NIH HHS R01GM97136
6 · The paper itself

Abstract

backgroundD-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.

conclusionOur 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.

Indexed as

Abnormalities, MultipleAdultAtaxiaAzoospermiaBase SequenceDNA Copy Number VariationsGene DosageHearing Loss, SensorineuralHeterozygoteHigh-Throughput Nucleotide SequencingHumansMaleMitochondrial DiseasesMolecular Diagnostic TechniquesMolecular Sequence DataPeroxisomal Multifunctional Protein-2HSD17B4 protein, humanPeroxisomal Multifunctional Protein-2

Identifiers

PMID24602372
PMCPMC4015298
OpenAlexW2171312763

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.