Dual diagnosis of UQCRFS1 -related mitochondrial complex III deficiency and recessive GJA8 -related cataracts.

Autor: Blue EE; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.; Institute for Public Health Genetics, University of Washington, Seattle, WA 98195, USA.; Brotman Baty Institute, Seattle, WA 98195, USA., Huang SJ; Department of Medical Genetics, Marshfield Clinic, Marshfield, WI 54449, USA., Khan A; Institute for Public Health Genetics, University of Washington, Seattle, WA 98195, USA., Golden-Grant K; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Boyd B; Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA., Rosenthal EA; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Gillentine MA; Department of Laboratories, Seattle Children's Hospital, Seattle, WA 98105, USA., Fleming LR; Department of Genetics, Saint Luke's Genetics and Metabolic Clinic, Boise, ID 83712, USA., Adams DR; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD 20892, USA., Wolfe L; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD 20892, USA., Allworth A; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Bamshad MJ; Brotman Baty Institute, Seattle, WA 98195, USA.; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Caruana NJ; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., Chanprasert S; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Chen J; Institute for Public Health Genetics, University of Washington, Seattle, WA 98195, USA., Dargie N; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Doherty D; Brotman Baty Institute, Seattle, WA 98195, USA.; Division of Developmental Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Friederich MW; Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA.; Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA., Hisama FM; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Horike-Pyne M; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Lee JC; Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA., Donovan TE; Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA., Hock DH; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia.; Victorian Clinical Genetics Services, Royal Children's Hospital, Parkville, VIC, Australia., Leppig KA; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Miller DE; Brotman Baty Institute, Seattle, WA 98195, USA.; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA., Mirzaa G; Brotman Baty Institute, Seattle, WA 98195, USA.; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA., Ranchalis J; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Raskind WH; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Michel CR; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Reisdorph R; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Schwarze U; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA., Sheppeard S; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Strohbehn S; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Stroud DA; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia.; Victorian Clinical Genetics Services, Royal Children's Hospital, Parkville, VIC, Australia., Sybert VP; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Wener MH; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.; Department of Rheumatology, University of Washington, Seattle, WA 98195, USA., Stergachis AB; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.; Brotman Baty Institute, Seattle, WA 98195, USA.; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA., Lam CT; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98105, USA., Jarvik GP; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.; Brotman Baty Institute, Seattle, WA 98195, USA.; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA., Dipple KM; Brotman Baty Institute, Seattle, WA 98195, USA.; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA 98105, USA., Van Hove JLK; Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA.; Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA., Glass IA; Brotman Baty Institute, Seattle, WA 98195, USA.; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Jazyk: angličtina
Zdroj: Rare (Amsterdam, Netherlands) [Rare] 2024; Vol. 2. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1016/j.rare.2024.100040
Abstrakt: Biallelic pathogenic variants in UQCRFS1 underlie a rare form of isolated mitochondrial complex III deficiency associated with lactic acidosis and a distinctive scalp alopecia previously described in two unrelated probands. Here, we describe a participant in the Undiagnosed Diseases Network (UDN) with a dual diagnosis of two autosomal recessive disorders revealed by genome sequencing: UQCRFS1 -related mitochondrial complex III deficiency and GJA8 -related cataracts. Both pathogenic variants have been reported before: UQCRFS1 (NM_006003.3:c.215-1 G>C, p.Val72_Thr81del10) in a case with mitochondrial complex III deficiency and GJA8 (NM 005267.5:c.736 G>T, p.Glu246*) as a somatic change in aged cornea leading to decreased junctional coupling. A multi-modal approach combining enzyme assays and cellular proteomics analysis provided clear evidence of complex III respiratory chain dysfunction and low abundance of the Rieske iron-sulfur protein, validating the pathogenic effect of the UQCRFS1 variant. This report extends the genotypic and phenotypic spectrum for these two rare disorders and highlights the utility of deep phenotyping and genomics data to achieve diagnosis and insights into rare disease.
Databáze: MEDLINE