A severe form of autosomal recessive spinocerebellar ataxia associated with novel PMPCA variants

Yoko Takahashi, Masaya Kubota, Rika Kosaki, Kenjiro Kosaki, Akira Ishiguro

研究成果: Article査読

抄録

Spinocerebellar ataxia, autosomal recessive 2 (SCAR2) [MIM:213200] is a rare autosomal recessive disease of spinocerebellar ataxia associated with degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. Recently, several PMPCA gene variants have been reported in SCAR2 patients with mild and non-progressive symptoms. PMPCA codes frataxin, which is crucial for iron biosynthesis in cells. We report a case of a 15-year-old Japanese girl with infancy-onset, very severe and progressive developmental delay, cerebellar ataxia, and extrapyramidal symptoms. Brain magnetic resonance imaging showed cerebellar atrophy and excessive brain iron accumulation in the bilateral globus pallidi and substantia nigra. Based on the clinical phenotypes and imaging, neurodegeneration with brain iron accumulation was suspected. Whole-exome sequencing on the proband and her parents revealed novel compound heterozygous variants at c.667C > T (p.Arg223Cys) and c.853del (p.Asp285llefs*16) in PMPCA. Thus, her disease was diagnosed as SCAR2. Phenotype in our case was different from ones previously reported for SCARs in the points of much severer clinical presentations with extrapyramidal signs and imaging suspected iron accumulation, and might overlap neurodegeneration with brain iron accumulation or NBIA subtypes. Our case might provide a new insight into PMPCA gene-related disorders and expand the disease concept.

本文言語English
ページ(範囲)464-469
ページ数6
ジャーナルBrain and Development
43
3
DOI
出版ステータスPublished - 2021 3

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

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