ClinVar Genomic variation as it relates to human health
NC_012920.1:m.8993T>C
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NC_012920.1:m.8993T>C
Variation ID: 9642 Accession: VCV000009642.39
- Type and length
-
single nucleotide variant, 1 bp
- Location
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MT: 8993 (GRCh38) [ NCBI UCSC ] MT: 8993 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 24, 2015 Apr 15, 2024 Feb 17, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNC_012920.1:m.8993T>C YP_003024031.1:p.Leu156Pro - Protein change
- Other names
- MTATP6, 8993T-C, LEU156PRO
- L156P
- Canonical SPDI
- NC_012920.1:8992:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
- Links
- ClinGen: CA120596
- Genetic Testing Registry (GTR): GTR000500595
- Genetic Testing Registry (GTR): GTR000556568
- Genetic Testing Registry (GTR): GTR000591967
- Genetic Testing Registry (GTR): GTR000591969
- Genetic Testing Registry (GTR): GTR000591975
- Genetic Testing Registry (GTR): GTR000591976
- OMIM: 516060.0002
- dbSNP: rs199476133
- VarSome
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MT-ATP6 | - | - | GRCh38 | 265 | 310 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, single submitter
|
- | RCV000010275.11 | |
Pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2007 | RCV000010276.5 | |
Pathogenic (2) |
reviewed by expert panel
|
Feb 17, 2021 | RCV000495030.2 | |
Pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2007 | RCV000754647.1 | |
Pathogenic (2) |
criteria provided, single submitter
|
Oct 17, 2019 | RCV000854390.2 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 23, 2020 | RCV001268873.1 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 4, 2022 | RCV002247300.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Feb 17, 2021)
|
reviewed by expert panel
Method: curation
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Mitochondrial disease
(Mitochondrial inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen
Accession: SCV001736752.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Comment:
The m.8993T>C (p.L156P) variant in MT-ATP6 has been reported in >16 individuals with primary mitochondrial disease with onset ranging from the first year of life … (more)
The m.8993T>C (p.L156P) variant in MT-ATP6 has been reported in >16 individuals with primary mitochondrial disease with onset ranging from the first year of life to adulthood; and who had features variably consistent with Leigh syndrome and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) (PS4; PMIDs: 8395787, 16532470, 30128709, 29101127, 28003964, 26265210, 22819295, 19046652, 18055910, 16049925, 10604142). Per our literature review and a recently published review, there are no published de novo occurrences of this variant (PMID: 30763462). This variant is located at the same amino acid position as another well-known pathogenic variant, m.8993T>G (p.L156R) (PM5). This variant segregated with disease in multiple affected members in multiple families and several healthy family members had lower to undetectable levels of the variant (PP1_moderate; PMID: 10604142). In silico tools predict this variant to be pathogenic (PP3). Cybrid studies (homoplasmic for this variant) showed reduced ATP production compared to Rho+ control cell lines (PS3_supporting; PMID: 19160410). In summary, this variant meets criteria to be classified as pathogenic for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel on February 17, 2021. Mitochondrial DNA-specific ACMG/AMP criteria applied: PS3_supporting, PS4, PM5, PP1_moderate, PP3). (less)
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Pathogenic
(May 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Leber optic atrophy
Affected status: unknown
Allele origin:
germline
|
Mendelics
Accession: SCV002517648.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Oct 17, 2019)
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criteria provided, single submitter
Method: clinical testing
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NARP syndrome
Affected status: unknown
Allele origin:
germline
|
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV000997425.1
First in ClinVar: Nov 02, 2019 Last updated: Nov 02, 2019 |
Comment:
The NC_012920.1:m.8993T>C (YP_003024031.1:p.Leu156Pro) variant in MTATP6 gene is interpretated to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the … (more)
The NC_012920.1:m.8993T>C (YP_003024031.1:p.Leu156Pro) variant in MTATP6 gene is interpretated to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PS1, PS3 (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Mitochondrial inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001448091.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Cerebellar ataxia (present) , Spastic paraplegia (present) , Polyneuropathy (present) , Crohn disease (present) , Graves disease (present) , Hypertonia (present) , Sensory neuropathy (present) … (more)
Cerebellar ataxia (present) , Spastic paraplegia (present) , Polyneuropathy (present) , Crohn disease (present) , Graves disease (present) , Hypertonia (present) , Sensory neuropathy (present) , Seizure (present) (less)
Sex: female
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Leigh syndrome
Affected status: yes
Allele origin:
maternal
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Pediatric Department, Xiangya Hospital, Central South University
Accession: SCV002761213.1
First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023 |
Clinical Features:
Abnormal basal ganglia MRI signal intensity (present) , Muscle weakness (present) , Easy fatigability (present)
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Pathogenic
(May 22, 2017)
|
no assertion criteria provided
Method: clinical testing
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Mitochondrial disease
Affected status: yes
Allele origin:
germline
|
Wellcome Centre for Mitochondrial Research, Newcastle University
Accession: SCV000577898.1
First in ClinVar: Jul 17, 2017 Last updated: Jul 17, 2017 |
Number of individuals with the variant: 1
Sex: male
|
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Pathogenic
(Dec 01, 2007)
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no assertion criteria provided
Method: literature only
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ATAXIA AND POLYNEUROPATHY, ADULT-ONSET
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000030500.3
First in ClinVar: Apr 04, 2013 Last updated: Feb 01, 2019 |
Comment on evidence:
In 4 sibs with mitochondrial complex V (ATP synthase) deficiency mitochondrial type 1 (MC5DM1; 500015) resulting in Leigh syndrome (see 256000), originally reported by van … (more)
In 4 sibs with mitochondrial complex V (ATP synthase) deficiency mitochondrial type 1 (MC5DM1; 500015) resulting in Leigh syndrome (see 256000), originally reported by van Erven et al. (1987), de Vries et al. (1993) found a T-to-C transition at nucleotide 8993 in the gene for ATPase 6. The mutation was predicted to cause a substitution of proline for leucine. The 4 sibs were severely affected and 1 of them died at the age of 17 years. The possibility of a mitochondrial basis was suggested by the fact that all children were affected; furthermore, beginning at the age of 56, the mother complained of weakness in her left leg, easy fatigability, and sensory disturbances in her feet. Neurologic examination demonstrated pyramidal signs in both legs, and ancillary investigations yielded results compatible with the diagnosis of Leigh syndrome. All patients, including the mother, were heteroplasmic for the mutation. The oldest of the 4 sibs died at age 17 after a progressive neurologic deterioration for 8 to 10 years. The other 3 sibs were living at ages 25, 23, and 20 years. Thus, the clinical picture did not agree strictly with that of infantile subacute necrotizing encephalopathy of Leigh. In the 3 living sibs there was no abnormality of pyruvate metabolism detected by study of serum and urine, but all 3 had marked elevation of CSF pyruvate and lactate concentration. Furthermore, pyruvate oxidation rates were normal in fibroblasts and leukocytes. A defect restricted to brain was suggested. Chakrapani et al. (1998) described another family with the 8993T-C mutation causing Leigh syndrome. A brother and sister were found to be homoplasmic for the 8993T-C mutation; the asymptomatic mother was heteroplasmic. The features in the boy were those of NARP (551500). Beside delayed motor development, ataxia, and raised CSF lactate, developmental regression followed acute illnesses in early childhood, with slow reacquisition of skills and pronounced ataxia thereafter. Fujii et al. (1998) reported a patient with Leigh syndrome with the 8993T-C mutation. They reviewed 9 other Leigh syndrome patients with the 8993T-C mutation and compared them with 18 reported cases with Leigh syndrome caused by the 8993T-G mutation (516060.0001). Leigh syndrome with the 8993T-C mutation was characterized by a significantly higher frequency of ataxia (P less than 0.01). None of the reviewed 8993T-C Leigh syndrome patients had retinitis pigmentosa, which is one of the characteristic findings in Leigh syndrome caused by the 8993T-G mutation. The milder symptoms of 8993T-C Leigh syndrome may be explained by the milder complex V dysfunction; however, the higher frequency of ataxia in association with 8993T-C requires more study. Vilarinho et al. (2001) reported 4 new 8993T-C patients. One was a 17-year-old girl with remitting-relapsing neurodegenerative disease since age 16 months which worsened during fevers or infectious disease. She had elevated CSF lactate and brain MRI was compatible with Leigh syndrome. Proton magnetic resonance spectroscopy showed slight elevation of lactate in the basal ganglia. Her mother and maternal aunt showed a progressive cerebellar ataxia. The second case was of a 16 year-old boy who experienced episodes of loss of consciousness and awkward gait during febrile illness in childhood with a slow recovery. Blood and CSF lactate concentrations were elevated. Brain MRI showed basal ganglia involvement. The third case was of a 21 year-old girl who experienced her first episode of lethargy and hypotonia at age 5 months during a fever. Similar episodes reappeared in her first 10 years. At age 11 years, examination showed mental deficiency, severe dysarthria, and vertical gaze palsy. Blood lactate was elevated. Brain MRI showed hyperlucencies in the putamen and head caudate nucleus. Two older sisters had peripheral neuropathy with normal MRI and blood lactate. The fourth case was of a 16 year-old cousin of case 3 who had a subacute episode of leg weakness, ataxia and dysarthria during a fever at age 3 years. She improved but had permanent motor disability. Similar episodes recurred and always had a slow recovery. At age 9 she had elevated blood and CSF lactate and brain MRI was compatible with maternally inherited Leigh syndrome. Debray et al. (2007) reported long-term follow-up on a patient who met the stringent criteria for Leigh syndrome established by Rahman et al. (1996). At age 4 years, the patient presented with respiratory distress, unexplained tachypnea, and a 2-day history of ptosis. On day 5 of hospitalization, he deteriorated with apnea and severe hypercapnia and required mechanical ventilation for 5 days. Ophthalmologic examination revealed nystagmus and supranuclear ophthalmoplegia. CT scan showed bilateral basal ganglia hypodensities. Blood lactate was 1.7 mmol/L (normal less than 2.2) and CSF lactate was 4.1 mmol/L (normal less than 1.8). He recovered without sequelae and functioned normally throughout childhood and early adolescence. Follow-up at age 18 revealed a slight cognitive decline in nonverbal tasks. The patient's leukocyte DNA revealed a greater than 95% 8993T-C mutant DNA; in contrast, the mutation was undetectable in his mother. Debray et al. (2007) reviewed 20 Leigh syndrome patients with the 8993T-C mutation. Only half (10/20) of the patients fulfilled the criteria of Rahman et al. (1996) for typical Leigh syndrome. Eighty-five percent (17/20) survived a median follow-up time of 16 years and 41% (7/20) did not have mental retardation. Debray et al. (2007) concluded that a favorable outcome can be observed in a significant percentage of Leigh syndrome patients with the 8993T-C mtDNA mutation. Rantamaki et al. (2005) reported 4 sibs with adult-onset ataxia and polyneuropathy (500010) and a heteroplasmic 8993T-C mutation. One of the sibs had early-onset severe ataxia and moderate mental impairment and died at age 22 years. The remaining 3 sibs had adult-onset of variable gait abnormalities, axonal sensorimotor polyneuropathy, abnormal eye movements, and dysarthria. Genetic analysis of the 3 surviving sibs showed mutant mtDNA ranging from 64 to 89%. Rantamaki et al. (2005) emphasized the unique phenotypic presentation in this family. Craig et al. (2007) identified a 3-generation family with slowly progressive adult-onset ataxia associated with the heteroplasmic 8993T-C mutation. A mother, daughter, and granddaughter were affected, with 86%, 82%, and 83% mutation heteroplasmy, respectively, in the blood. Other features included cerebellar dysarthria, axonal sensory neuropathy, and gaze-evoked horizontal nystagmus. The daughter and granddaughter reported intermittent exacerbations of ataxia, associated with migraine in 1 case. The daughter had optic atrophy without retinal degeneration. The 8993T-C mutation was not identified in 191 additional patients with episodic ataxia, 307 patients with ataxia, or 96 patients with suspected Charcot-Marie-Tooth disease (see, e.g., CMT1A; 118220) suggesting that it is not a common finding in these phenotypic conditions. (less)
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Pathogenic
(Dec 01, 2007)
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no assertion criteria provided
Method: literature only
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MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, MITOCHONDRIAL TYPE 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000030499.3
First in ClinVar: Apr 04, 2013 Last updated: Feb 01, 2019 |
Comment on evidence:
In 4 sibs with mitochondrial complex V (ATP synthase) deficiency mitochondrial type 1 (MC5DM1; 500015) resulting in Leigh syndrome (see 256000), originally reported by van … (more)
In 4 sibs with mitochondrial complex V (ATP synthase) deficiency mitochondrial type 1 (MC5DM1; 500015) resulting in Leigh syndrome (see 256000), originally reported by van Erven et al. (1987), de Vries et al. (1993) found a T-to-C transition at nucleotide 8993 in the gene for ATPase 6. The mutation was predicted to cause a substitution of proline for leucine. The 4 sibs were severely affected and 1 of them died at the age of 17 years. The possibility of a mitochondrial basis was suggested by the fact that all children were affected; furthermore, beginning at the age of 56, the mother complained of weakness in her left leg, easy fatigability, and sensory disturbances in her feet. Neurologic examination demonstrated pyramidal signs in both legs, and ancillary investigations yielded results compatible with the diagnosis of Leigh syndrome. All patients, including the mother, were heteroplasmic for the mutation. The oldest of the 4 sibs died at age 17 after a progressive neurologic deterioration for 8 to 10 years. The other 3 sibs were living at ages 25, 23, and 20 years. Thus, the clinical picture did not agree strictly with that of infantile subacute necrotizing encephalopathy of Leigh. In the 3 living sibs there was no abnormality of pyruvate metabolism detected by study of serum and urine, but all 3 had marked elevation of CSF pyruvate and lactate concentration. Furthermore, pyruvate oxidation rates were normal in fibroblasts and leukocytes. A defect restricted to brain was suggested. Chakrapani et al. (1998) described another family with the 8993T-C mutation causing Leigh syndrome. A brother and sister were found to be homoplasmic for the 8993T-C mutation; the asymptomatic mother was heteroplasmic. The features in the boy were those of NARP (551500). Beside delayed motor development, ataxia, and raised CSF lactate, developmental regression followed acute illnesses in early childhood, with slow reacquisition of skills and pronounced ataxia thereafter. Fujii et al. (1998) reported a patient with Leigh syndrome with the 8993T-C mutation. They reviewed 9 other Leigh syndrome patients with the 8993T-C mutation and compared them with 18 reported cases with Leigh syndrome caused by the 8993T-G mutation (516060.0001). Leigh syndrome with the 8993T-C mutation was characterized by a significantly higher frequency of ataxia (P less than 0.01). None of the reviewed 8993T-C Leigh syndrome patients had retinitis pigmentosa, which is one of the characteristic findings in Leigh syndrome caused by the 8993T-G mutation. The milder symptoms of 8993T-C Leigh syndrome may be explained by the milder complex V dysfunction; however, the higher frequency of ataxia in association with 8993T-C requires more study. Vilarinho et al. (2001) reported 4 new 8993T-C patients. One was a 17-year-old girl with remitting-relapsing neurodegenerative disease since age 16 months which worsened during fevers or infectious disease. She had elevated CSF lactate and brain MRI was compatible with Leigh syndrome. Proton magnetic resonance spectroscopy showed slight elevation of lactate in the basal ganglia. Her mother and maternal aunt showed a progressive cerebellar ataxia. The second case was of a 16 year-old boy who experienced episodes of loss of consciousness and awkward gait during febrile illness in childhood with a slow recovery. Blood and CSF lactate concentrations were elevated. Brain MRI showed basal ganglia involvement. The third case was of a 21 year-old girl who experienced her first episode of lethargy and hypotonia at age 5 months during a fever. Similar episodes reappeared in her first 10 years. At age 11 years, examination showed mental deficiency, severe dysarthria, and vertical gaze palsy. Blood lactate was elevated. Brain MRI showed hyperlucencies in the putamen and head caudate nucleus. Two older sisters had peripheral neuropathy with normal MRI and blood lactate. The fourth case was of a 16 year-old cousin of case 3 who had a subacute episode of leg weakness, ataxia and dysarthria during a fever at age 3 years. She improved but had permanent motor disability. Similar episodes recurred and always had a slow recovery. At age 9 she had elevated blood and CSF lactate and brain MRI was compatible with maternally inherited Leigh syndrome. Debray et al. (2007) reported long-term follow-up on a patient who met the stringent criteria for Leigh syndrome established by Rahman et al. (1996). At age 4 years, the patient presented with respiratory distress, unexplained tachypnea, and a 2-day history of ptosis. On day 5 of hospitalization, he deteriorated with apnea and severe hypercapnia and required mechanical ventilation for 5 days. Ophthalmologic examination revealed nystagmus and supranuclear ophthalmoplegia. CT scan showed bilateral basal ganglia hypodensities. Blood lactate was 1.7 mmol/L (normal less than 2.2) and CSF lactate was 4.1 mmol/L (normal less than 1.8). He recovered without sequelae and functioned normally throughout childhood and early adolescence. Follow-up at age 18 revealed a slight cognitive decline in nonverbal tasks. The patient's leukocyte DNA revealed a greater than 95% 8993T-C mutant DNA; in contrast, the mutation was undetectable in his mother. Debray et al. (2007) reviewed 20 Leigh syndrome patients with the 8993T-C mutation. Only half (10/20) of the patients fulfilled the criteria of Rahman et al. (1996) for typical Leigh syndrome. Eighty-five percent (17/20) survived a median follow-up time of 16 years and 41% (7/20) did not have mental retardation. Debray et al. (2007) concluded that a favorable outcome can be observed in a significant percentage of Leigh syndrome patients with the 8993T-C mtDNA mutation. Rantamaki et al. (2005) reported 4 sibs with adult-onset ataxia and polyneuropathy (500010) and a heteroplasmic 8993T-C mutation. One of the sibs had early-onset severe ataxia and moderate mental impairment and died at age 22 years. The remaining 3 sibs had adult-onset of variable gait abnormalities, axonal sensorimotor polyneuropathy, abnormal eye movements, and dysarthria. Genetic analysis of the 3 surviving sibs showed mutant mtDNA ranging from 64 to 89%. Rantamaki et al. (2005) emphasized the unique phenotypic presentation in this family. Craig et al. (2007) identified a 3-generation family with slowly progressive adult-onset ataxia associated with the heteroplasmic 8993T-C mutation. A mother, daughter, and granddaughter were affected, with 86%, 82%, and 83% mutation heteroplasmy, respectively, in the blood. Other features included cerebellar dysarthria, axonal sensory neuropathy, and gaze-evoked horizontal nystagmus. The daughter and granddaughter reported intermittent exacerbations of ataxia, associated with migraine in 1 case. The daughter had optic atrophy without retinal degeneration. The 8993T-C mutation was not identified in 191 additional patients with episodic ataxia, 307 patients with ataxia, or 96 patients with suspected Charcot-Marie-Tooth disease (see, e.g., CMT1A; 118220) suggesting that it is not a common finding in these phenotypic conditions. (less)
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Pathogenic
(Feb 22, 2024)
|
no assertion criteria provided
Method: clinical testing
|
NARP syndrome
(Mitochondrial inheritance)
Affected status: yes
Allele origin:
maternal
|
Undiagnosed Diseases Network, NIH
Study: Undiagnosed Diseases Network (NIH), UDN
Accession: SCV004812018.1 First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
Clinical Features:
Generalized hypotonia (present) , Hammertoe (present) , Gait ataxia (present) , Delayed gross motor development (present) , Positive Romberg sign (present) , Falls (present) , … (more)
Generalized hypotonia (present) , Hammertoe (present) , Gait ataxia (present) , Delayed gross motor development (present) , Positive Romberg sign (present) , Falls (present) , Obstructive sleep apnea syndrome (present) , Somatic sensory dysfunction (present) , Poor hand-eye coordination (present) (less)
Age: 10-19 years
Sex: male
Ethnicity/Population group: Mexican,Taiwanese
Tissue: Blood
|
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not provided
(-)
|
no classification provided
Method: literature only
|
Leigh syndrome
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000188894.5
First in ClinVar: Sep 09, 2014 Last updated: Oct 01, 2022 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Mitochondrial DNA-Associated Leigh Syndrome and NARP. | Adam MP | - | 2023 | PMID: 20301352 |
Episodic ataxia and hemiplegia caused by the 8993T->C mitochondrial DNA mutation. | Craig K | Journal of medical genetics | 2007 | PMID: 18055910 |
Adult-onset ataxia and polyneuropathy caused by mitochondrial 8993T-->C mutation. | Rantamäki MT | Annals of neurology | 2005 | PMID: 16049925 |
Clinical and molecular findings in four new patients harbouring the mtDNA 8993T>C mutation. | Vilarinho L | Journal of inherited metabolic disease | 2001 | PMID: 11916326 |
A family with Leigh syndrome caused by the rarer T8993C mutation. | Chakrapani A | Journal of inherited metabolic disease | 1998 | PMID: 9762610 |
Phenotypic differences between T-->C and T-->G mutations at nt 8993 of mitochondrial DNA in Leigh syndrome. | Fujii T | Pediatric neurology | 1998 | PMID: 9568930 |
Isolated case of mental retardation and ataxia due to a de novo mitochondrial T8993G mutation. | de Coo IF | American journal of human genetics | 1996 | PMID: 8644724 |
Leigh syndrome: clinical features and biochemical and DNA abnormalities. | Rahman S | Annals of neurology | 1996 | PMID: 8602753 |
Clinical, biochemical, and molecular analysis of a maternally inherited case of Leigh syndrome (MILS) associated with the mtDNA T8993G point mutation. | Degoul F | Journal of inherited metabolic disease | 1995 | PMID: 8750605 |
A T-->C mutation at nt 8993 of mitochondrial DNA in a child with Leigh syndrome. | Santorelli FM | Neurology | 1994 | PMID: 8190310 |
A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's syndrome. | de Vries DD | Annals of neurology | 1993 | PMID: 8395787 |
Familial Leigh's syndrome: association with a defect in oxidative metabolism probably restricted to brain. | van Erven PM | Journal of neurology | 1987 | PMID: 3612192 |
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Text-mined citations for rs199476133 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.