NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 8, 2017
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002316190.9

Allele description [Variation Report for NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup)]

NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup)

Genes:

LOC109610631:aristaless related homeobox polyalanine expansion region [Gene]
ARX:aristaless related homeobox [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

Xp21.3

Genomic location:

Preferred name:

NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup)

Other names:

NP_620689.1:p.(Ala109_Ala115dup)

HGVS:

NC_000023.11:g.25013662CGC[17]
NG_008281.1:g.7260GGC[17]
NG_052655.1:g.233CGC[17]
NM_139058.3:c.306GGC[17]MANE SELECT
NP_620689.1:p.Ala109_Ala115dup
NC_000023.10:g.25031776_25031777insGCCGCCGCCGCCGCCGCCGCC
NC_000023.10:g.25031779CGC[17]
NM_139058.2:c.315_335dupGGCGGCGGCGGCGGCGGCGGC
NM_139058.3:c.315_335dupMANE SELECT

Links:

OMIM: 300382.0001; dbSNP: rs387906492

NCBI 1000 Genomes Browser:

rs387906492

Molecular consequence:

NM_139058.3:c.306GGC[17] - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000851643	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 8, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11889467, 15533998, 21496008, 23583054 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000851643

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 8, 2017)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy.

Strømme P, Mangelsdorf ME, Shaw MA, Lower KM, Lewis SM, Bruyere H, Lütcherath V, Gedeon AK, Wallace RH, Scheffer IE, Turner G, Partington M, Frints SG, Fryns JP, Sutherland GR, Mulley JC, Gécz J.

Nat Genet. 2002 Apr;30(4):441-5. Epub 2002 Mar 11.

PubMed [citation]

PMID:: 11889467

A polyalanine tract expansion in Arx forms intranuclear inclusions and results in increased cell death.

Nasrallah IM, Minarcik JC, Golden JA.

J Cell Biol. 2004 Nov 8;167(3):411-6.

PubMed [citation]

PMID:: 15533998
PMCID:: PMC2172475

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000851643.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The c.315_335dup21 pathogenic mutation (also known as p.A109_A115dup), located in coding exon 2 of the ARX gene, results from an in-frame duplication of 21 nucleotides at nucleotide positions 315 to 335. This results in the duplication of 7 extra residues (AAAAAAA) between codons 109 and 115, leading to an expansion of the first polyalanine tract from 16 to 23. This mutation was originally reported as (GCG)10+7 in two families with X-linked infantile spasm syndrome and West syndrome (Strømme et al. Nat Genet. 2002 Apr;30(4):441-5). De novo occurrences of the mutation (described as c.333_334ins[GCG]7 and c.333_335dup(GGC)7) were also reported in multiple patients with mental retardation, dystonia, infantile-onset refractory epilepsy, and/or developmental delay (Guerrini et al. Neurology. 2007 Jul 31;69(5):427-33; Mirzaa et al. Pediatr. Neurol. 2013 May;48(5):367-77). In addition, expression of ARX protein harboring the 23 alanines was shown to cause protein aggregation, cell death, and mislocalization (Nasrallah et al. J Cell Biol. 2004 Nov 8;167(3):411-6; Fullston et al. Clin. Genet. 2011 Dec;80(6):510-22). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine