Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss caused by a mutation in RRM2B.

Autor: Roberts L; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Julius S; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Dawlat S; Department of Human Genetics, National Health Laboratory Servicexs, Groote Schuur Hospital, Cape Town, South Africa., Yildiz S; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Rebello G; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Meldau S; Department of Human Genetics, National Health Laboratory Servicexs, Groote Schuur Hospital, Cape Town, South Africa.; Division of Chemical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa., Pillay K; Division of Anatomical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa., Esterhuizen A; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Department of Human Genetics, National Health Laboratory Servicexs, Groote Schuur Hospital, Cape Town, South Africa., Vorster A; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Benefeld G; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., da Rocha J; Sydney Brenner Institute for Molecular Bioscience, Division of Human Genetics, National Health Laboratory Service, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Beighton P; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Sellars SL; Division of Otorhinolaryngology, Department of Surgery, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Thandrayen K; Department of Paediatrics, Chris Hani Baragwanath Academic Hospital and School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Pettifor JM; Department of Paediatrics, Chris Hani Baragwanath Academic Hospital and School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Ramesar RS; UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2020 Nov; Vol. 41 (11), pp. 1871-1876. Date of Electronic Publication: 2020 Sep 09.
DOI: 10.1002/humu.24094
Abstrakt: More than two decades ago, a recessive syndromic phenotype affecting kidneys, eyes, and ears, was first described in the endogamous Afrikaner population of South Africa. Using whole-exome sequencing of DNA from two affected siblings (and their carrier parents), we identified the novel RRM2B c.786G>T variant as a plausible disease-causing mutation. The RRM2B gene is involved in mitochondrial integrity, and the observed change was not previously reported in any genomic database. The subsequent screening revealed the variant in two newly presenting unrelated patients, as well as two patients in our registry with rod-cone dystrophy, hearing loss, and Fanconi-type renal disease. All patients with the c.786G>T variant share an identical 1.5 Mb haplotype around this gene, suggesting a founder effect in the Afrikaner population. We present ultrastructural evidence of mitochondrial impairment in one patient, to support our thesis that this RRM2B variant is associated with the renal, ophthalmological, and auditory phenotype.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
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