Bcs1l mutations produce fanconi syndrome with developmental disability

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. Access through your institution Buy or subscribe This is a preview of subscription

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MITOCHONDRIAL COQ10 DEFICIENCY WITH CARDIOMYOPATHY AND GASTROINTESTINAL OBSTRUCTION Article Open access 03 May 2024 NOVEL _CLTC_ VARIANTS CAUSE NEW BRAIN AND KIDNEY PHENOTYPES Article 07

July 2021 FURTHER DELINEATION OF DEFECTS IN MRPS2 CAUSING HUMAN OXPHOS DEFICIENCY AND EARLY DEVELOPMENTAL ABNORMALITIES IN ZEBRAFISH Article Open access 13 May 2025 REFERENCES * Klootwijk

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deficiency in fatal influenza encephalopathy. Brain Dev. 2012;34:115–7. Article  Google Scholar  Download references FUNDING 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. AUTHOR INFORMATION Author notes * These authors

contributed equally: Kojima-Ishii Kanako, Nana Sakakibara. AUTHORS AND AFFILIATIONS * Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Kojima-Ishii Kanako, Yuko Ichimiya & Yuichi Mushimoto * Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan Nana Sakakibara, Tomoko Horinouchi, China

Nagano, Tomohiko Yamamura, Kazumoto Iijima & Kandai Nozu * Center for Medical Genetics and Department of Metabolism, Chiba Children’s Hospital, Chiba, Japan Kei Murayama * Department of

Pediatrics, Uwajima City Hospital, Uwajima, Japan Koji Nagatani & Satoshi Murata * Center for Intractable Diseases, Saitama Medical University Hospital, Saitama, Japan Akira Otake *

Department of Pediatrics & Clinical Genomics, Faculty of Medicine, Saitama Medical University, Saitama, Japan Akira Otake * Department of Pediatrics and Child Health, Kurume University

Graduate School of Medicine, Kurume, Japan Yasutoshi Koga * Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan Hisato Suzuki, Tomoko Uehara & Kenjiro Kosaki *

Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Atomic Bomb Disease Institute, Nagasaki, Japan Koh-ichiro Yoshiura & Hiroyuki Mishima Authors *

Kojima-Ishii Kanako View author publications You can also search for this author inPubMed Google Scholar * Nana Sakakibara View author publications You can also search for this author

inPubMed Google Scholar * Kei Murayama View author publications You can also search for this author inPubMed Google Scholar * Koji Nagatani View author publications You can also search for

this author inPubMed Google Scholar * Satoshi Murata View author publications You can also search for this author inPubMed Google Scholar * Akira Otake View author publications You can also

search for this author inPubMed Google Scholar * Yasutoshi Koga View author publications You can also search for this author inPubMed Google Scholar * Hisato Suzuki View author publications

You can also search for this author inPubMed Google Scholar * Tomoko Uehara View author publications You can also search for this author inPubMed Google Scholar * Kenjiro Kosaki View author

publications You can also search for this author inPubMed Google Scholar * Koh-ichiro Yoshiura View author publications You can also search for this author inPubMed Google Scholar * Hiroyuki

Mishima View author publications You can also search for this author inPubMed Google Scholar * Yuko Ichimiya View author publications You can also search for this author inPubMed Google

Scholar * Yuichi Mushimoto View author publications You can also search for this author inPubMed Google Scholar * Tomoko Horinouchi View author publications You can also search for this

author inPubMed Google Scholar * China Nagano View author publications You can also search for this author inPubMed Google Scholar * Tomohiko Yamamura View author publications You can also

search for this author inPubMed Google Scholar * Kazumoto Iijima View author publications You can also search for this author inPubMed Google Scholar * Kandai Nozu View author publications

You can also search for this author inPubMed Google Scholar CONTRIBUTIONS K-I K, NS, and KN: conception or design; K-I K, NS, KM, AO, and YK: data collection and analysis; K-I K and NS: data

interpretation. HS, TU, KK, K-I Y, and HM: WES analysis and interpretation; K-I K, KN, SM, YI and YM: collection of patient samples and clinical information; K-I K and NS: drafting the

article; TH, CN, TY, and KI: critical revision of the article. All authors approved the final version of the manuscript for publication. CORRESPONDING AUTHOR Correspondence to Nana

Sakakibara. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ETHICAL APPROVAL All procedures involving human participants were in accordance with the

ethical standards of the Institutional Review Board of Kobe University Graduate School of Medicine (IRB approval number 301), the Kurume University Institutional Review Board (IRB approval

number 273), the Kyushu University Institutional Review Board (IRB approval number 667-00), and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Written informed consent was obtained from all individuals participating in this study. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional

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permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kanako, KI., Sakakibara, N., Murayama, K. _et al._ _BCS1L_ mutations produce Fanconi syndrome with developmental disability. _J Hum Genet_

67, 143–148 (2022). https://doi.org/10.1038/s10038-021-00984-0 Download citation * Received: 04 April 2021 * Revised: 07 September 2021 * Accepted: 01 October 2021 * Published: 15 October

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