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NC_012920.1(MT-TL1):m.3249G>A AND Kearns-Sayre syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 11, 2010
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:
RCV000010222.6

Allele description [Variation Report for NC_012920.1(MT-TL1):m.3249G>A]

NC_012920.1(MT-TL1):m.3249G>A

Gene:
MT-TL1:mitochondrially encoded tRNA leucine 1 (UUA/G) [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Genomic location:
Preferred name:
NC_012920.1(MT-TL1):m.3249G>A
HGVS:
NC_012920.1:m.3249G>A
Nucleotide change:
3249G-A
Links:
OMIM: 590050.0011; dbSNP: rs199474667
NCBI 1000 Genomes Browser:
rs199474667

Condition(s)

Name:
Kearns-Sayre syndrome
Synonyms:
Ophthalmoplegia, pigmentary degeneration of retina, and cardiomyopathy; Oculocraniosomatic syndrome; Ophthalmoplegia plus syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010787; MedGen: C0022541; Orphanet: 480; OMIM: 530000

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000030446OMIM
no assertion criteria provided
Uncertain significance
(Jun 11, 2010) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A new mitochondrial point mutation in the transfer RNA(Leu) gene in a patient with a clinical phenotype resembling Kearns-Sayre syndrome.

Seneca S, Verhelst H, De Meirleir L, Meire F, Ceuterick-De Groote C, Lissens W, Van Coster R.

Arch Neurol. 2001 Jul;58(7):1113-8. Review.

PubMed [citation]
PMID:
11448301

Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription.

Yakubovskaya E, Mejia E, Byrnes J, Hambardjieva E, Garcia-Diaz M.

Cell. 2010 Jun 11;141(6):982-93. doi: 10.1016/j.cell.2010.05.018.

PubMed [citation]
PMID:
20550934
PMCID:
PMC2887341

Details of each submission

From OMIM, SCV000030446.5

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

Description

This variant, formerly titled KEARNS-SAYRE SYNDROME, has been reclassified as a variant of unknown significance because its pathogenicity has not been confirmed.

Seneca et al. (2001) reported a male patient with clinical signs suggestive of Kearns-Sayre syndrome (530000), including onset at age 22 years of progressive visual failure with retinopathy, external ophthalmoplegia, sensorineural hearing loss, exercise intolerance, muscle weakness, and difficulty swallowing. Skeletal muscle analysis showed decreased activity of complex I and numerous ragged-red fibers. A heteroplasmic 3249G-A point mutation was found in the MTTL1 gene, with a high percentage of mutant mtDNA in skeletal muscle (85%) and in leukocytes (45%). The patient's mother carried less than 5% mutant mtDNA in her blood.

Yakubovskaya et al. (2010) found that 3249G formed a double hydrogen bond with arg387 of MTERF1 (602318). The 3249G-A mutation eliminated this interaction and significantly interfered with transcriptional termination by MTERF1.

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

Last Updated: Oct 8, 2024