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Molecular diagnosis of mitochondrial respiratory chain disorders in J apan: Focusing on mitochondrial DNA depletion syndrome
Author(s) -
Yamazaki Taro,
Murayama Kei,
Compton Alison G,
Sugiana Canny,
Harashima Hiroko,
Amemiya Shin,
Ajima Masami,
Tsuruoka Tomoko,
Fujinami Ayako,
Kawachi Emi,
Kurashige Yoshiko,
Matsushita Kenshi,
Wakiguchi Hiroshi,
Mori Masato,
Iwasa Hiroyasu,
Okazaki Yasushi,
Thorburn David R,
Ohtake Akira
Publication year - 2014
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.12249
Subject(s) - medicine , mitochondrial dna , mitochondrial disease , polymerase chain reaction , mitochondrial respiratory chain , mutation , mitochondrion , gene , genetics , biology
Background Although mitochondrial respiratory chain disorders ( MRCD ) are one of the most common congenital metabolic diseases, there is no cumulative data on enzymatic diagnosis and clinical manifestation for MRCD in J apan and A sia. Methods We evaluated 675 Japanese patients having profound lactic acidemia, or patients having symptoms or signs of multiple‐organ origin simultaneously without lactic acidemia on respiratory chain enzyme activity assay and blue native polyacrylamide gel electrophoresis. Quantitative polymerase chain reaction was used to diagnose mitochondrial DNA depletion syndrome ( MTDPS ). Mutation analysis of several genes responsible for MTDPS was also performed. Results A total of 232 patients were diagnosed with a probable or definite MRCD . MRCD are common, afflicting one in every several thousand people in J apan. More than one in 10 of the patients diagnosed lacked lactic acidemia. A subsequent analysis of the causative genes of MTDPS identified novel mutations in six of the patients. A 335 bp deletion in deoxyguanosine kinase ( DGUOK ; g.11692_12026del335 (p. A48fsX 90)) was noted in two unrelated families, and may therefore be a common mutation in Japanese people. The proportion of all patients with MTDPS , and particularly those with recessive DNA polymerase γ ( POLG ) mutations, appears to be lower in J apan than in other studies. This is most likely due to the relatively high prevalence of ancient E uropean POLG mutations in C aucasian populations. No other significant differences were identified in a comparison of the enzymatic diagnoses, disease classifications or prognoses in Japanese and C aucasian patients with MRCD . Conclusion MTDPS and other MRCD are common, but serious, diseases that occur across all races.