NM_000414.4(HSD17B4):c.1538C>T (p.Pro513Leu) AND Perrault syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 18, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000125467.3

Allele description [Variation Report for NM_000414.4(HSD17B4):c.1538C>T (p.Pro513Leu)]

NM_000414.4(HSD17B4):c.1538C>T (p.Pro513Leu)

Gene:

HSD17B4:hydroxysteroid 17-beta dehydrogenase 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q23.1

Genomic location:

Preferred name:

NM_000414.4(HSD17B4):c.1538C>T (p.Pro513Leu)

HGVS:

NC_000005.10:g.119525250C>T
NG_008182.1:g.77798C>T
NM_000414.4:c.1538C>TMANE SELECT
NM_001199291.3:c.1613C>T
NM_001199292.2:c.1484C>T
NM_001292027.2:c.1466C>T
NM_001292028.2:c.1118C>T
NP_000405.1:p.Pro513Leu
NP_001186220.1:p.Pro538Leu
NP_001186221.1:p.Pro495Leu
NP_001278956.1:p.Pro489Leu
NP_001278957.1:p.Pro373Leu
NC_000005.9:g.118860945C>T
NM_000414.3:c.1538C>T

Protein change:

P373L; PRO513LEU

Links:

OMIM: 601860.0012; dbSNP: rs587777444

NCBI 1000 Genomes Browser:

rs587777444

Molecular consequence:

NM_000414.4:c.1538C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001199291.3:c.1613C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001199292.2:c.1484C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001292027.2:c.1466C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001292028.2:c.1118C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Perrault syndrome 1 (PRLTS1)
Synonyms:: GONADAL DYSGENESIS, XX TYPE, WITH DEAFNESS; Ovarian dysgenesis with sensorineural deafness
Identifiers:: MONDO: MONDO:0009300; MedGen: C4551721; Orphanet: 2855; OMIM: 233400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000168919	OMIM	no assertion criteria provided	Pathogenic (Mar 18, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000168919

OMIM

no assertion criteria provided

Pathogenic
(Mar 18, 2014)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Peroxisomal D-bifunctional protein deficiency: three adults diagnosed by whole-exome sequencing.

Lines MA, Jobling R, Brady L, Marshall CR, Scherer SW, Rodriguez AR, Lee L, Lang AE, Mestre TA, Wanders RJ, Ferdinandusse S, Tarnopolsky MA; Canadian Pediatric Genetic Disorders Sequencing Consortium (FORGE Canada)..

Neurology. 2014 Mar 18;82(11):963-8. doi: 10.1212/WNL.0000000000000219. Epub 2014 Feb 19.

PubMed [citation]

PMID:: 24553428
PMCID:: PMC3963001

Details of each submission

From OMIM, SCV000168919.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 3 Italian sibs, including 2 sisters, with Perrault syndrome (PRLTS1; 233400), Lines et al. (2014) identified compound heterozygous mutations in the HSD17B4 gene: a c.1537C-A transversion, resulting in a pro513-to-leu (P513L) substitution, and a c.1628G-C transversion, resulting in an arg543-to-pro (R543P; 601860.0013) substitution. The mutations, which were found by whole-exome sequencing, occurred at highly conserved residues within the active site of the hydratase domain and segregated with the disorder in the family. They were filtered against the dbSNP, 1000 Genomes Project, and Exome Variant Server databases, as well as 130 local control exomes. Immunoblot analysis of patient cells showed markedly reduced DBP enoyl-CoA hydratase activity, as well as absence of the 45-kD posttranslational fragment containing the hydratase domain. Laboratory studies of all patients showed increased serum total bile acids, but phytanic and very long-chain fatty acids were normal. Patient fibroblasts showed decreased beta-oxidation of pristanic acid. Peroxisome morphology was normal.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 7, 2022

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