NM_006554.5(MTX2):c.295_296del (p.Ser98_Leu99insTer) AND Mandibuloacral dysplasia progeroid syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 16, 2020
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:: RCV001270625.1

Allele description [Variation Report for NM_006554.5(MTX2):c.295_296del (p.Ser98_Leu99insTer)]

NM_006554.5(MTX2):c.295_296del (p.Ser98_Leu99insTer)

Gene:

MTX2:metaxin 2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

2q31.1

Genomic location:

Preferred name:

NM_006554.5(MTX2):c.295_296del (p.Ser98_Leu99insTer)

HGVS:

NC_000002.12:g.176328300CT[1]
NC_000002.12:g.176328300_176328301CT[1]
NM_001006635.3:c.265_266del
NM_001319097.2:c.295_296del
NM_001319098.2:c.295_296del
NM_006554.5:c.295_296delMANE SELECT
NP_001006636.1:p.Ser88_Leu89insTer
NP_001306026.1:p.Ser98_Leu99insTer
NP_001306027.1:p.Ser98_Leu99insTer
NP_006545.1:p.Ser98_Leu99insTer
NC_000002.11:g.177193028CT[1]
NM_006554.4:c.294_295delTC
NM_006554.4:c.295_296del

Links:

OMIM: 608555.0005; dbSNP: rs768727228

NCBI 1000 Genomes Browser:

rs768727228

Molecular consequence:

NM_001006635.3:c.265_266del - nonsense - [Sequence Ontology: SO:0001587]
NM_001319097.2:c.295_296del - nonsense - [Sequence Ontology: SO:0001587]
NM_001319098.2:c.295_296del - nonsense - [Sequence Ontology: SO:0001587]
NM_006554.5:c.295_296del - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

Uncertain function

Condition(s)

Name:: Mandibuloacral dysplasia progeroid syndrome
Identifiers:: MONDO: MONDO:0030880; MedGen: C5436867; OMIM: 619127

Recent activity

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Homo sapiens cDNA clone IMAGE:5267863
Homo sapiens cDNA clone IMAGE:5267863
gi|66267555|gb|BC094790.1|

Nucleotide
Homo sapiens cDNA FLJ43635 fis, clone SPLEN2037580
Homo sapiens cDNA FLJ43635 fis, clone SPLEN2037580
gi|34531777|dbj|AK125623.1|

Nucleotide
telomere-associated protein RIF1 isoform X12 [Homo sapiens]
telomere-associated protein RIF1 isoform X12 [Homo sapiens]
gi|2462574748|ref|XP_054198735.1|

Protein
telomere-associated protein RIF1 isoform X5 [Homo sapiens]
telomere-associated protein RIF1 isoform X5 [Homo sapiens]
gi|2462574727|ref|XP_054198725.1|

Protein
PREDICTED: Homo sapiens replication timing regulatory factor 1 (RIF1), transcrip...
PREDICTED: Homo sapiens replication timing regulatory factor 1 (RIF1), transcript variant X35, misc_RNA
gi|2462574749|ref|XR_008486440.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001451355	OMIM	no assertion criteria provided	Pathogenic (Dec 16, 2020)	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

SCV001451355

OMIM

no assertion criteria provided

Pathogenic
(Dec 16, 2020)

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 MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology.

Elouej S, Harhouri K, Le Mao M, Baujat G, Nampoothiri S, Kayserili H, Menabawy NA, Selim L, Paneque AL, Kubisch C, Lessel D, Rubinsztajn R, Charar C, Bartoli C, Airault C, Deleuze JF, Rötig A, Bauer P, Pereira C, Loh A, Escande-Beillard N, Muchir A, et al.

Nat Commun. 2020 Sep 11;11(1):4589. doi: 10.1038/s41467-020-18146-9. Erratum in: Nat Commun. 2020 Oct 19;11(1):5349. doi: 10.1038/s41467-020-19290-y.

PubMed [citation]

PMID:: 32917887
PMCID:: PMC7486921

Details of each submission

From OMIM, SCV001451355.1

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

Description

In an Ecuadorian boy (patient 5) with mandibuloacral dysplasia progeroid syndrome (MDPS; 619127), Elouej et al. (2020) identified a homozygous 2-bp deletion (c.294_295delTC, NM_006554.4) in exon 6 of the MTX2 gene, resulting in a leu99-to-ter (L99X) substitution. The mutation was identified by whole-exome sequencing. The variant was not found in the dbSNP (build 144), 1000 Genomes Project, Exome Variant Server, or gnomAD databases. The parents were not known to be consanguineous but they were born in the same region of Ecuador; in addition, the patient's exome data showed regions of homozygosity (ROH) totaling 34 Mb, suggesting ancient inbreeding. The MTX2 mutation was located within the largest autosomal ROH of 5 Mb.

#	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: Jul 15, 2024

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