BCS1L mutations produce Fanconi syndrome with developmental disability
- 15 October 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Human Genetics
- Vol. 67 (3), 143-148
- https://doi.org/10.1038/s10038-021-00984-0
Abstract
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.Keywords
Funding Information
- Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology of Japan
This publication has 31 references indexed in Scilit:
- Severe renal tubulopathy in a newborn due to BCS1L gene mutation: Effects of different treatment modalities on the clinical courseGene, 2013
- Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cellsMitochondrion, 2012
- Molecular Diagnosis of Infantile Mitochondrial Disease with Targeted Next-Generation SequencingScience Translational Medicine, 2012
- COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafnessJCI Insight, 2011
- A Loss-of-Function Mutation in NaPi-IIa and Renal Fanconi's SyndromeThe New England Journal of Medicine, 2010
- COQ2 NephropathyJournal of the American Society of Nephrology, 2007
- Diagnostic criteria for respiratory chain disorders in adults and childrenNeurology, 2002
- Melatonin protects against 6‐OHDA‐induced neurotoxicity in rats: a role for mitochondrial complex I activityThe FASEB Journal, 2000
- Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndromeNature Genetics, 1997
- Leigh syndrome: Clinical features and biochemical and DNA abnormalitiesAnnals of Neurology, 1996