NM_004177.5(STX3):c.372_373dup (p.Arg125fs) AND Retinal dystrophy and microvillus inclusion disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 21, 2021
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:: RCV001542244.1

Allele description [Variation Report for NM_004177.5(STX3):c.372_373dup (p.Arg125fs)]

NM_004177.5(STX3):c.372_373dup (p.Arg125fs)

Gene:

STX3:syntaxin 3 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11q12.1

Genomic location:

Preferred name:

NM_004177.5(STX3):c.372_373dup (p.Arg125fs)

HGVS:

NC_000011.10:g.59792119TC[3]
NG_047082.1:g.42061TC[3]
NM_001178040.2:c.372_373dup
NM_004177.5:c.372_373dupMANE SELECT
NP_001171511.1:p.Arg125fs
NP_004168.1:p.Arg125fs
NC_000011.9:g.59559592TC[3]

Protein change:

R125fs

Links:

OMIM: 600876.0003; dbSNP: rs2135015231

NCBI 1000 Genomes Browser:

rs2135015231

Molecular consequence:

NM_001178040.2:c.372_373dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004177.5:c.372_373dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Retinal dystrophy and microvillus inclusion disease
Identifiers:: MONDO: MONDO:0859170; MedGen: C5561943; OMIM: 619446

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001760913	OMIM	no assertion criteria provided	Pathogenic (Jul 21, 2021)	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

SCV001760913

OMIM

no assertion criteria provided

Pathogenic
(Jul 21, 2021)

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

Loss of syntaxin 3 causes variant microvillus inclusion disease.

Wiegerinck CL, Janecke AR, Schneeberger K, Vogel GF, van Haaften-Visser DY, Escher JC, Adam R, Thöni CE, Pfaller K, Jordan AJ, Weis CA, Nijman IJ, Monroe GR, van Hasselt PM, Cutz E, Klumperman J, Clevers H, Nieuwenhuis EE, Houwen RH, van Haaften G, Hess MW, Huber LA, et al.

Gastroenterology. 2014 Jul;147(1):65-68.e10. doi: 10.1053/j.gastro.2014.04.002. Epub 2014 Apr 12.

PubMed [citation]

PMID:: 24726755

Details of each submission

From OMIM, SCV001760913.1

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

Description

By whole-exome sequencing in an 18-month-old Pakistani boy (patient 2) with intractable diarrhea due to microvillus inclusion disease, who later developed progressive retinal dystrophy (RDMVID; 619446), Wiegerinck et al. (2014) identified homozygosity for a 2-bp duplication (c.372_373dup) in exon 6 of the STX3 gene, causing a frameshift predicted to result in a premature termination codon (Arg125LeufsTer7). Sanger sequencing confirmed the mutation and its segregation with disease in the family. The mutation was predicted to cause protein depletion and truncation, which was supported by Western blot of STX3 on patient organoids. Stable expression of a truncated version of STX3 corresponding to the patient's mutant protein in Caco2 cell cultures recapitulated all histologic hallmarks of the disease, including a statistically significant increase of both microvillus inclusions and basolateral microvilli. Scanning and transmission electron microscopy of the mutant Caco2 cells further demonstrated disruption of cell polarity, with formation of intercellular lumina within the cell multilayer.

#	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: Dec 24, 2023

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