Case of maternal uniparental isodisomy with autosomal recessive Alport syndrome combined with congenital myasthenia and Oguchi disease.

Uniparental isodisomy (UPiD) is a genetic condition in which an individual inherits two identical copies of a chromosome, or part of a chromosome, from one parent. UPiD can result in the development of autosomal recessive disorders if the chromosome inherited from one parent has a pathogenic variant. Herein, we present a 20 year-old female patient who had no significant family history including kidney, muscular, or ocular diseases. She had muscle weakness since infancy and was suspected with congenital myasthenia. She was diagnosed with Oguchi disease, a congenital condition characterized by night blindness, by an ophthalmologist. At 3 years of age, hematuria was noted, and gross hematuria was occasionally observed thereafter. Exome analysis revealed homozygous variants in the COL4A4, CHRND, and SAG genes on chromosome 2, which are the causative genes of Alport syndrome, congenital myasthenic syndrome, and Oguchi disease, respectively. Array comparative genomic hybridization analysis and microsatellite analysis revealed maternal UPiD. At approximately 18 years of age, she presented with proteinuria with mild kidney impairment, and kidney biopsy was performed at 20 years of age. Type IV collagen α5 chain staining showed a weak but positive image in the glomerular basement membrane. However, thinning and irregular thickening of the glomerular basement membrane and reticular changes in the dense layer were observed, which were consistent with Alport syndrome. Angiotensin II receptor blocker (candesartan) was administered, and her urinary protein levels decreased. She had a homozygous missense variant, positive α5 chain staining, and a mild phenotype.