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NM_012062.5(DNM1L):c.1085G>A (p.Gly362Asp) AND Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jan 1, 2015
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:
RCV000239637.3

Allele description [Variation Report for NM_012062.5(DNM1L):c.1085G>A (p.Gly362Asp)]

NM_012062.5(DNM1L):c.1085G>A (p.Gly362Asp)

Gene:
DNM1L:dynamin 1 like [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p11.21
Genomic location:
Preferred name:
NM_012062.5(DNM1L):c.1085G>A (p.Gly362Asp)
HGVS:
  • NC_000012.12:g.32731019G>A
  • NG_012219.1:g.56817G>A
  • NM_001278463.2:c.1085G>A
  • NM_001278464.2:c.1124G>A
  • NM_001278465.2:c.1124G>A
  • NM_001278466.2:c.476G>A
  • NM_001330380.2:c.1124G>A
  • NM_005690.5:c.1085G>A
  • NM_012062.5:c.1085G>AMANE SELECT
  • NM_012063.4:c.1085G>A
  • NP_001265392.1:p.Gly362Asp
  • NP_001265393.1:p.Gly375Asp
  • NP_001265394.1:p.Gly375Asp
  • NP_001265395.1:p.Gly159Asp
  • NP_001317309.1:p.Gly375Asp
  • NP_005681.2:p.Gly362Asp
  • NP_005681.2:p.Gly362Asp
  • NP_036192.2:p.Gly362Asp
  • NP_036193.2:p.Gly362Asp
  • NC_000012.11:g.32883953G>A
  • NM_005690.4:c.1085G>A
  • NM_012062.4:c.1085G>A
  • O00429:p.Gly362Asp
Protein change:
G159D; GLY362ASP
Links:
UniProtKB: O00429#VAR_076316; OMIM: 603850.0002; dbSNP: rs879255685
NCBI 1000 Genomes Browser:
rs879255685
Molecular consequence:
  • NM_001278463.2:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278464.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278465.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278466.2:c.476G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330380.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005690.5:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012062.5:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012063.4:c.1085G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1
Synonyms:
Encephalopathy due to defective mitochondrial and peroxisomal fission 1
Identifiers:
MONDO: MONDO:0013726; MedGen: C3280660; Orphanet: 330050; OMIM: 614388

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000298164OMIM
no assertion criteria provided
Pathogenic
(Oct 15, 2010)
germlineliterature only

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

SCV000965723Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
criteria provided, single submitter

(ACMG Guidelines, 2007)
Likely pathogenic
(Jan 1, 2015)
de novoclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

DNM1L-related mitochondrial fission defect presenting as refractory epilepsy.

Vanstone JR, Smith AM, McBride S, Naas T, Holcik M, Antoun G, Harper ME, Michaud J, Sell E, Chakraborty P, Tetreault M; Care4Rare Consortium., Majewski J, Baird S, Boycott KM, Dyment DA, MacKenzie A, Lines MA.

Eur J Hum Genet. 2016 Jul;24(7):1084-8. doi: 10.1038/ejhg.2015.243. Epub 2015 Nov 25.

PubMed [citation]
PMID:
26604000
PMCID:
PMC5070894

A lethal de novo mutation in the middle domain of the dynamin-related GTPase Drp1 impairs higher order assembly and mitochondrial division.

Chang CR, Manlandro CM, Arnoult D, Stadler J, Posey AE, Hill RB, Blackstone C.

J Biol Chem. 2010 Oct 15;285(42):32494-503. doi: 10.1074/jbc.M110.142430. Epub 2010 Aug 9.

PubMed [citation]
PMID:
20696759
PMCID:
PMC2952251
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000298164.1

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

Description

In a 7-year-old boy, born of unrelated Caucasian parents, with encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1; 614388), Vanstone et al. (2016) identified a de novo heterozygous c.1085G-A transition (c.1085G-A, NM_012062.4) in exon 10 of the DNM1L gene, resulting in a gly362-to-asp (G362D) substitution in the middle domain, which is involved in homo-oligomerization. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the ExAC database. The patient had severely delayed psychomotor development and onset of refractory epilepsy at about 1 year of age. Confocal microscopy of patient fibroblasts showed hyperfusion of the mitochondrial network. However, respiratory chain enzymologies in muscle and skin fibroblasts and lactate/pyruvate ratio in fibroblasts were normal, as was serum lactate. There was no evidence of peroxisomal dysfunction. Vanstone et al. (2016) noted the diagnostic difficulties given that this patient had no clinical evidence of mitochondrial dysfunction on standard screening tests, and suggested that the disorder may result from abnormal mitochondrial distribution within neurons. Functional studies of the variant were not performed, but Vanstone et al. (2016) noted that Chang et al. (2010) had demonstrated that a mutation in an adjacent residue (G363D) compromised higher-order assembly and polymerization-dependent GTPase activity, suggesting pathogenicity.

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

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000965723.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024