TY - JOUR
T1 - BCS1L mutations produce Fanconi syndrome with developmental disability
AU - Kanako, Kojima Ishii
AU - Sakakibara, Nana
AU - Murayama, Kei
AU - Nagatani, Koji
AU - Murata, Satoshi
AU - Otake, Akira
AU - Koga, Yasutoshi
AU - Suzuki, Hisato
AU - Uehara, Tomoko
AU - Kosaki, Kenjiro
AU - Yoshiura, Koh ichiro
AU - Mishima, Hiroyuki
AU - Ichimiya, Yuko
AU - Mushimoto, Yuichi
AU - Horinouchi, Tomoko
AU - Nagano, China
AU - Yamamura, Tomohiko
AU - Iijima, Kazumoto
AU - Nozu, Kandai
N1 - Funding Information:
This study was supported by Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (subject ID: 19K17297 to NS, 17H04189 to KI, 19K08726 to KN, and 18K07892 to YK). This study was also supported partly by the Japan Agency for Medical Research and Development, Grant/Award Numbers: JP17ek0109088 and JP19ek0109336 to YK.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to The Japan Society of Human Genetics.
PY - 2022/3
Y1 - 2022/3
N2 - Fanconi syndrome is a functional disorder of the proximal tubule, characterized by pan-aminoaciduria, glucosuria, hypophosphatemia, and metabolic acidosis. With the advancements in gene analysis technologies, several causative genes are identified for Fanconi syndrome. Several mitochondrial diseases cause Fanconi syndrome and various systemic symptoms; however, it is rare that the main clinical symptoms in such disorders are Fanconi syndrome without systematic active diseases like encephalomyopathy or cardiomyopathy. In this study, we analyzed two families exhibiting Fanconi syndrome, developmental disability and mildly elevated liver enzyme levels. Whole-exome sequencing (WES) detected compound heterozygous known and novel BCS1L mutations, which affect the assembly of mitochondrial respiratory chain complex III, in both cases. The pathogenicity of these mutations has been established in several mitochondria-related functional analyses in this study. Mitochondrial diseases with isolated renal symptoms are uncommon; however, this study indicates that mitochondrial respiratory chain complex III deficiency due to BCS1L mutations cause Fanconi syndrome with developmental disability as the primary indications.
AB - Fanconi syndrome is a functional disorder of the proximal tubule, characterized by pan-aminoaciduria, glucosuria, hypophosphatemia, and metabolic acidosis. With the advancements in gene analysis technologies, several causative genes are identified for Fanconi syndrome. Several mitochondrial diseases cause Fanconi syndrome and various systemic symptoms; however, it is rare that the main clinical symptoms in such disorders are Fanconi syndrome without systematic active diseases like encephalomyopathy or cardiomyopathy. In this study, we analyzed two families exhibiting Fanconi syndrome, developmental disability and mildly elevated liver enzyme levels. Whole-exome sequencing (WES) detected compound heterozygous known and novel BCS1L mutations, which affect the assembly of mitochondrial respiratory chain complex III, in both cases. The pathogenicity of these mutations has been established in several mitochondria-related functional analyses in this study. Mitochondrial diseases with isolated renal symptoms are uncommon; however, this study indicates that mitochondrial respiratory chain complex III deficiency due to BCS1L mutations cause Fanconi syndrome with developmental disability as the primary indications.
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U2 - 10.1038/s10038-021-00984-0
DO - 10.1038/s10038-021-00984-0
M3 - Article
C2 - 34650211
AN - SCOPUS:85117209314
VL - 67
SP - 143
EP - 148
JO - Jinrui idengaku zasshi. The Japanese journal of human genetics
JF - Jinrui idengaku zasshi. The Japanese journal of human genetics
SN - 1434-5161
IS - 3
ER -