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A novel homozygous CHMP1A variant arising from segmental uniparental disomy causes pontocerebellar hypoplasia type 8.
Sakamoto, Masamune; Shiiki, Toshihide; Matsui, Shuji; Okamoto, Nobuhiko; Koshimizu, Eriko; Tsuchida, Naomi; Uchiyama, Yuri; Hamanaka, Kohei; Fujita, Atsushi; Miyatake, Satoko; Misawa, Kazuharu; Mizuguchi, Takeshi; Matsumoto, Naomichi.
Afiliação
  • Sakamoto M; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Shiiki T; Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Matsui S; Department of Pediatrics, Tokyo Children Rehabilitation Hospital, Tokyo, Japan.
  • Okamoto N; Department of Pediatrics, Tokyo Children Rehabilitation Hospital, Tokyo, Japan.
  • Koshimizu E; Department of Medical Genetics, Osaka Women's and Children's Hospital, Izumi, Japan.
  • Tsuchida N; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Uchiyama Y; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Hamanaka K; Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan.
  • Fujita A; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Miyatake S; Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan.
  • Misawa K; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Mizuguchi T; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Matsumoto N; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
J Hum Genet ; 68(4): 247-253, 2023 Apr.
Article em En | MEDLINE | ID: mdl-36509868
ABSTRACT
Pontocerebellar hypoplasia (PCH) is currently classified into 16 subgroups. Using mostly next-generation sequencing, pathogenic variants have been identified in as many as 24 PCH-associated genes. PCH type 8 (PCH8) is a rare heterogeneous disorder. Its clinical presentation includes severe development delay, increased muscle tone, microcephaly, and magnetic resonance imaging (MRI) abnormalities such as reduced cerebral white matter, a thin corpus callosum, and brainstem and cerebellar hypoplasia. To date, only two variants in the CHMP1A gene (MIM 164010), NM_002768.5 c.88 C > T (p.Glu30*) and c.28-13 G > A, have been identified homozygously in seven patients with PCH8 from four families (MIM 614961). CHMP1A is a subunit of the endosomal sorting complex required for transport III (ESCRT-III), which regulates the formation and release of extracellular vesicles. Biallelic CHMP1A loss of function impairs the ESCRT-III-mediated release of extracellular vesicles, which causes impaired progenitor proliferation in the developing brain. Herein, we report a patient with PCH8 who had a homozygous CHMP1A variant, c.122delA (p.Asn41Metfs*2), which arose from segmental uniparental disomy. Although our patient had similar MRI findings to those of previously reported patients, with no progression, we report some novel neurological and developmental findings that expand our knowledge of the clinical consequences associated with CHMP1A variants.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Cerebelares / Microcefalia Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Humans Idioma: En Revista: J Hum Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Cerebelares / Microcefalia Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Humans Idioma: En Revista: J Hum Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Japão