作者: Noam Shomron , Alexander Lossos , Alan R Shuldiner , Zohar Argov , Claudia Gonzaga-Jauregui
DOI: 10.1111/CGE.13929
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摘要: POLR3A encodes the largest subunit of DNA-dependent RNA polymerase III. Pathogenic variants in this gene are associated with dysregulation tRNA production and other non-coding RNAs. POLR3A-related disorders include variable phenotypes. The genotype-phenotype correlation is still unclear. Phenotypic analysis exome sequencing were performed four affected siblings diagnosed clinically hereditary spastic ataxia, two healthy their unaffected mother. All (ages 46-55) had similar clinical features early childhood-onset hypodontia adolescent-onset progressive ataxia. None progeria, gonadal dysfunction or dysmorphism. individuals biallelic pathogenic composed by cis-acting intronic splicing-altering variants, c.1909 + 22G > A c.3337-11 T C. wild-type alleles. mother another sibling heterozygous for allele containing both variants. This first report addressing consequence homozygosity a unique gene. was previously reported compound combinations patients Wiedemann-Rautenstrauch syndrome, severe progeroid POLR3A-associated phenotype. We show that ataxia hypodontia, not features. These findings contribute to characterization disorders.