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Genetic, metabolic and clinical delineation of an MRPS23-associated mitochondrial disorder.
Ittiwut, Chupong; Ittiwut, Rungnapa; Kuptanon, Chulaluck; Matsuhashi, Tetsuro; Shimura, Masaru; Sugiyama, Yohei; Onuki, Takanori; Ohtake, Akira; Murayama, Kei; Vatanavicharn, Nithiwat; Dejputtawat, Waralee; Tantisirivit, Nitchanund; Kor-Anantakul, Phawin; Kamolvisit, Wuttichart; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk.
Afiliação
  • Ittiwut C; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Ittiwut R; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand.
  • Kuptanon C; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Matsuhashi T; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand.
  • Shimura M; Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, Thailand.
  • Sugiyama Y; Center for Medical Genetics and Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
  • Onuki T; Center for Medical Genetics and Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
  • Ohtake A; Center for Medical Genetics and Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
  • Murayama K; Center for Medical Genetics and Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
  • Vatanavicharn N; Center for Intractable Diseases, Saitama Medical University Hospital, Saitama, Japan.
  • Dejputtawat W; Center for Medical Genetics and Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
  • Tantisirivit N; Division of Medical Genetics, Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • Kor-Anantakul P; Division of Growth and Development, Department of Pediatrics, Nakornping Hospital, Chiang Mai, Thailand.
  • Kamolvisit W; Department of Pediatrics, Nan Hospital, Nan, Thailand.
  • Suphapeetiporn K; Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Shotelersuk V; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand.
Sci Rep ; 13(1): 22005, 2023 12 12.
Article em En | MEDLINE | ID: mdl-38086984
ABSTRACT
MRPS23 is a nuclear gene encoding a mitochondrial ribosomal protein. A patient with a mitochondrial disorder was found to carry a variant in MRPS23. More cases are necessary to establish MRPS23 as a mitochondrial disease gene. Of 5134 exomes performed in our center, we identified five independent patients who had similar clinical manifestations and were homozygous for the same germline variant c.119C>T; p.P40L in MRPS23. Detailed clinical findings, mitochondrial enzyme activity assays from cultured skin fibroblasts, PCR-Sanger-sequencing, and variant age estimation were performed. Their available family members were also studied. Eight members homozygous for the MRPS23 p.P40L were identified. All were from Hmong hilltribe. Seven presented with alteration of consciousness and recurrent vomiting, while the eighth who was a younger brother of a proband was found pre-symptomatically. Patients showed delayed growth and development, hearing impairment, hypoglycemia, lactic acidosis, and liver dysfunction. In vitro assays of cultured fibroblasts showed combined respiratory chain complex deficiency with low activities of complexes I and IV. PCR-Sanger-sequencing confirmed the variant, which was estimated to have occurred 1550 years ago. These results establish the MRPS23-associated mitochondrial disorder inherited in an autosomal recessive pattern and provide insight into its clinical and metabolic features.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Acidose Láctica / Doenças Mitocondriais Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Acidose Láctica / Doenças Mitocondriais Idioma: En Ano de publicação: 2023 Tipo de documento: Article