Evidence map›Paper›PMID 20673864›Full record

ArticleAmerican journal of human genetics2010

Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome.

Sarah B Pierce, Tom Walsh, Karen M Chisholm, Ming K Lee, Anne M Thornton, Agata Fiumara, John M Opitz, Ephrat Levy-Lahad, Rachel E Klevit, Mary-Claire King

Open access · bronzeAbstract read
In one paragraph

Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 1 pooled it
10.9field-weighted citation impact, top 1% 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

128 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.

  1. International journal of molecular sciences · 2025
    Pooled it
  2. Review
  3. Neurology. Genetics · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. HSD17B4 mutation: an unusual cause of cerebellar ataxia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Article
  10. Article
  11. Disorders of fatty acid homeostasis.Journal of inherited metabolic disease · 2025
    Review
  12. Premature ovarian insufficiency.Nature reviews. Disease primers · 2024
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. A Homozygous Missense Variant inMolecular syndromology · 2024
    Article
  18. Article
  19. The peroxisome: an update on mysteries 3.0.Histochemistry and cell biology · 2024
    Review
  20. Review

68 more citing papers are in PubMed but not listed here.

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

10 authors at 5 institutions in 3 countries.

Sarah B PierceDepartment of Medicine, University of Washington, Seattle, WA 98195, USA.
Tom Walsh
Karen M Chisholm
Ming K Lee
Anne M Thornton
Agata Fiumara
John M Opitz
Ephrat Levy-Lahad
Rachel E Klevit
Mary-Claire King
University of Washington Medical Center · USUniversity of Washington · USHebrew University of Jerusalem · ILUniversity of Catania · ITUniversity of Utah · US

Funding

Genetics of Hearing Loss in Middle Eastern FamiliesR01DC005641 · NIDCD · UNIVERSITY OF WASHINGTON · PI KING, MARY-CLAIRE · 2003 to 2010
$4.4M
NIDCD NIH HHS R01 DC005641NIDCD NIH HHS R01DC005641
6 · The paper itself

Abstract

Perrault syndrome is a recessive disorder characterized by ovarian dysgenesis in females, sensorineural deafness in both males and females, and in some patients, neurological manifestations. No genes for Perrault syndrome have heretofore been identified. A small family of mixed European ancestry includes two sisters with well-characterized Perrault syndrome. Whole-exome sequencing of genomic DNA from one of these sisters revealed exactly one gene with two rare functional variants: HSD17B4, which encodes 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4), also known as D-bifunctional protein (DBP). HSD17B4/DBP is a multifunctional peroxisomal enzyme involved in fatty acid beta-oxidation and steroid metabolism. Both sisters are compound heterozygotes for HSD17B4 c.650A>G (p.Y217C) (maternal allele) and HSB17B4 c.1704T>A (p.Y568X) (paternal allele). The missense mutation is predicted by structural analysis to destabilize the HSD17B4 dehydrogenase domain. The nonsense mutation leads to very low levels of HSD17B4 transcript. Expression of mutant HSD17B4 protein in a compound heterozygote was severely reduced. Mutations in HSD17B4 are known to cause DBP deficiency, an autosomal-recessive disorder of peroxisomal fatty acid beta-oxidation that is generally fatal within the first two years of life. No females with DBP deficiency surviving past puberty have been reported, and ovarian dysgenesis has not previously been associated with this illness. Six other families with Perrault syndrome have wild-type sequences of HSD17B4. These results indicate that Perrault syndrome and DBP deficiency overlap clinically; that Perrault syndrome is genetically heterogeneous; that DBP deficiency may be underdiagnosed; and that whole-exome sequencing can reveal critical genes in small, nonconsanguineous families.

Indexed as

17-Hydroxysteroid DehydrogenasesAmino Acid SequenceAtaxiaBase SequenceDNA Mutational AnalysisExonsFemaleGene Expression Regulation, EnzymologicGonadal DysgenesisHearing LossHeterozygoteHumansHydro-LyasesMaleMolecular Sequence DataMutant Proteins17-Hydroxysteroid DehydrogenasesHSD17B4 protein, humanHydro-LyasesMutant ProteinsPeroxisomal Multifunctional Protein-2

Identifiers

PMID20673864
PMCPMC2917704
OpenAlexW2071965243

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.