NC_000006.12:g.45341183_45446148dup AND Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 7, 2013
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:: RCV000033220.5

Allele description [Variation Report for NC_000006.12:g.45341183_45446148dup]

NC_000006.12:g.45341183_45446148dup

Genes:

LOC129996578:ATAC-STARR-seq lymphoblastoid silent region 17265 [Gene]
SUPT3H:SPT3 homolog, SAGA and STAGA complex component [Gene - OMIM - HGNC]
LOC109611589:runt related transcription factor 2 polyalanine expansion region [Gene]
RUNX2:RUNX family transcription factor 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NC_000006.12:g.45341183_45446148dup

HGVS:

NC_000006.12:g.45341183_45446148dup
NC_000006.11:g.45308920_45413885dup

Note:

105-kb genomic duplication of exons 3 to 5 in RUNX2 plus flanking intronic sequences.

Nucleotide change:

105-KB DUP, EX3-5

Links:

dbVar: nssv7487210; dbVar: nsv1197544; OMIM: 600211.0014

Condition(s)

Name:: Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome
Synonyms:: Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly; METAPHYSEAL DYSPLASIA AND MAXILLARY HYPOPLASIA WITH OR WITHOUT BRACHYDACTYLY
Identifiers:: MONDO: MONDO:0007984; MedGen: C3549874; Orphanet: 2504; OMIM: 156510

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000057072	OMIM	no assertion criteria provided	Pathogenic (Feb 7, 2013)	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

SCV000057072

OMIM

no assertion criteria provided

Pathogenic
(Feb 7, 2013)

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

Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly is caused by a duplication in RUNX2.

Moffatt P, Ben Amor M, Glorieux FH, Roschger P, Klaushofer K, Schwartzentruber JA, Paterson AD, Hu P, Marshall C; FORGE Canada Consortium., Fahiminiya S, Majewski J, Beaulieu CL, Boycott KM, Rauch F.

Am J Hum Genet. 2013 Feb 7;92(2):252-8. doi: 10.1016/j.ajhg.2012.12.001. Epub 2013 Jan 3.

PubMed [citation]

PMID:: 23290074
PMCID:: PMC3567275

Details of each submission

From OMIM, SCV000057072.4

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

Description

In affected members from a 4-generation French Canadian family with metaphyseal dysplasia with maxillary hypoplasia without brachydactyly (MDMHB; 156510), Moffatt et al. (2013) identified heterozygosity for a 105-kb duplication (chr6:45,308,920-45,413,885, GRCh37) containing exons 3 to 5 of the RUNX2 gene. The duplication of exons 3 to 5 was confirmed with cDNA derived from a patient fibroblast line, and was not found in unaffected family members. Functional analysis of the corresponding duplication in mouse Runx2 in HEK293 cells demonstrated markedly increased protein levels for the mutant compared to wildtype, as well as increased transactivation activity for mutant Runx2.

#	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: Oct 14, 2023

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