Mitochondrial "dysmorphology" in variant classification.
Hum Genet
; 141(1): 55-64, 2022 Jan.
Article
em En
| MEDLINE
| ID: mdl-34750646
ABSTRACT
Mitochondrial disorders are challenging to diagnose. Exome sequencing has greatly enhanced the diagnostic precision of these disorders although interpreting variants of uncertain significance (VUS) remains a formidable obstacle. Whether specific mitochondrial morphological changes can aid in the classification of these variants is unknown. Here, we describe two families (four patients), each with a VUS in a gene known to affect the morphology of mitochondria through a specific role in the fission-fusion balance. In the first, the missense variant in MFF, encoding a fission factor, was associated with impaired fission giving rise to a characteristically over-tubular appearance of mitochondria. In the second, the missense variant in DNAJA3, which has no listed OMIM phenotype, was associated with fragmented appearance of mitochondria consistent with its published deficiency states. In both instances, the highly specific phenotypes allowed us to upgrade the classification of the variants. Our results suggest that, in select cases, mitochondrial "dysmorphology" can be helpful in interpreting variants to reach a molecular diagnosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Mitocondriais
/
Proteínas Mitocondriais
/
Proteínas de Choque Térmico HSP40
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Dinâmica Mitocondrial
/
Proteínas de Membrana
/
Mitocôndrias
Tipo de estudo:
Diagnostic_studies
Limite:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Hum Genet
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Arábia Saudita