NM_001145853.1(WFS1):c.2648_2651del (p.Phe883fs) AND Wolfram syndrome 1

Clinical significance:Pathogenic (Last evaluated: May 4, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000191146.4

Allele description [Variation Report for NM_001145853.1(WFS1):c.2648_2651del (p.Phe883fs)]

NM_001145853.1(WFS1):c.2648_2651del (p.Phe883fs)

Gene:
WFS1:wolframin ER transmembrane glycoprotein [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
4p16.1
Genomic location:
Preferred name:
NM_001145853.1(WFS1):c.2648_2651del (p.Phe883fs)
HGVS:
  • NC_000004.12:g.6302443_6302446del
  • NG_011700.1:g.37594_37597del
  • NM_001145853.1:c.2648_2651del
  • NP_001139325.1:p.Phe883fs
  • LRG_1417:g.37594_37597del
  • NC_000004.11:g.6304168_6304171delTTTC
  • NC_000004.11:g.6304170_6304173del
  • NM_006005.3:c.2648_2651delTCTTMANE SELECT
  • p.F883Sfs*68
Protein change:
F883fs
Links:
OMIM: 606201.0012; dbSNP: rs797045076
NCBI 1000 Genomes Browser:
rs797045076
Molecular consequence:
  • NM_001145853.1:c.2648_2651del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Wolfram syndrome 1 (WFS1)
Synonyms:
DIDMOAD syndrome
Identifiers:
MONDO: MONDO:0009101; MedGen: C4551693; Orphanet: 3463; OMIM: 222300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000024952OMIMno assertion criteria providedPathogenic
(Feb 1, 2001)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000245555Baylor Genetics - Adult_WEScriteria provided, single submitter
Pathogenic
(May 4, 2015)
paternal, germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

PMID:10521293

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1.

Hardy C, Khanim F, Torres R, Scott-Brown M, Seller A, Poulton J, Collier D, Kirk J, Polymeropoulos M, Latif F, Barrett T.

Am J Hum Genet. 1999 Nov;65(5):1279-90.

PubMed [citation]
PMID:
10521293
PMCID:
PMC1288280

Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation.

Sam W, Qin H, Crawford B, Yue D, Yu S.

Clin Genet. 2001 Feb;59(2):136-8. No abstract available.

PubMed [citation]
PMID:
11260218
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000024952.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

Hardy et al. (1999) and Sam et al. (2001) described Wolfram syndrome (WFS1; 222300) with a distinctive phenotype, namely, central respiratory failure: the patients were homozygous for a 4-bp (TCTT) deletion at position 2648-2651 in exon 8 of the WFS1 gene. The deletion caused loss of codon 883 and a frameshift, producing a 949-amino acid WFS1 protein, which was 59 amino acids longer than normal. The mutation changed the last 7 amino acids of the C terminus of the protein, leaving the transmembrane domains intact. In the patient with the 4-bp deletion reported by Hardy et al. (1999), there was severe brainstem atrophy and central respiratory failure requiring tracheostomy. Her affected sister had died at age 28 from brainstem atrophy and central respiratory failure. Five patients (from 3 families) who were heterozygous for the 4-bp deletion did not have respiratory failure. The 33-year-old patient reported by Sam et al. (2001) was diagnosed as having diabetes mellitus, a neurogenic bladder, and bilateral optic atrophy at the age of 10, 13, and 15, respectively. Audiometry was normal, and there was no evidence of diabetes insipidus. After an episode of respiratory arrest at age 32, she required intubation, ventilation, and subsequently, tracheostomy. MRI scan showed marked brainstem atrophy.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics - Adult_WES, SCV000245555.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing
(GTR000508680.4)
PubMed (2)
2Causasians1not providednot providedclinical testing
(GTR000508680.4)
PubMed (2)

Description

This variant has been previously reported as disease-causing and was found once in our laboratory in trans with a missense variant [C755R] in a 38-year-old female with Asperger, ataxia, optic atrophy, progressive vision impairment, spastic bladder, chronic fatigue, irregular menses. Variant is pathogenic in recessive state. Found once in our laboratory heterozygous in a 48-year-old male with type 2 diabetes and family history of sudden death.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyesnot providednot providednot provided
(GTR000508680.4)
1not provided1not provided
2germlineunknownnot providednot providednot provided
(GTR000508680.4)
1not provided1not provided

Last Updated: Jul 20, 2021

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