Biallelic Loss-of-Function NDUFA12 Variants Cause a Wide Phenotypic Spectrum from Leigh/Leigh-Like Syndrome to Isolated Optic Atrophy.
Mov Disord Clin Pract
; 9(2): 218-228, 2022 Feb.
Article
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| MEDLINE
| ID: mdl-35141356
ABSTRACT
BACKGROUND:
Biallelic loss-of-function NDUFA12 variants have hitherto been linked to mitochondrial complex I deficiency presenting with heterogeneous clinical and radiological features in nine cases only.OBJECTIVES:
To fully characterize, both phenotypically and genotypically, NDUFA12-related mitochondrial disease.METHODS:
We collected data from cases identified by screening genetic databases of several laboratories worldwide and systematically reviewed the literature.RESULTS:
Nine unreported NDUFA12 cases from six pedigrees were identified, with presentation ranging from movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. MRI showed basal ganglia abnormalities (n = 6), optic atrophy (n = 2), or was unremarkable (n = 1). All carried homozygous truncating NDUFA12 variants, three of which are novel.CONCLUSIONS:
Our case series expands phenotype-genotype correlations in NDUFA12-associated mitochondrial disease, providing evidence of intra- and inter-familial clinical heterogeneity for the same variant. It confirms NDUFA12 variants should be included in the diagnostic workup of Leigh/Leigh-like syndromes - particularly with dystonia - as well as isolated optic atrophy.
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MEDLINE
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En
Revista:
Mov Disord Clin Pract
Año:
2022
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Article