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Novel homoplasmic mutation in the mitochondrial tRNA Tyr gene associated with atypical mitochondrial cytopathy presenting with focal segmental glomerulosclerosis
Author(s) -
Scaglia Fernando,
Vogel Hannes,
Hawkins Edith P.,
Vladutiu Georgirene D.,
Liu LingLing,
Wong LeeJun C.
Publication year - 2003
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.20315
Subject(s) - mitochondrial dna , transfer rna , mutation , gene , mitochondrion , genetics , focal segmental glomerulosclerosis , biology , rna , kidney , glomerulonephritis
Abstract We report a 9‐year‐old girl with a mitochondrial cytopathy preceded by steroid‐resistant focal segmental glomerulosclerosis (FSGS). The proband presented at the age of 2 years with steroid‐resistant nephrotic syndrome caused by FSGS. Her renal function progressively deteriorated and a dilated cardiomyopathy developed at the age of 7 years. A skeletal muscle biopsy showed a combined respiratory chain (RC) defect and a partial deficiency of coenzyme Q 10 . A novel mutation in the evolutionary highly conserved region of the mitochondrial tRNA Tyr gene was found in homoplasmic state in skeletal muscle, blood, and renal tissue. The mutation was also found in homoplasmic state in her mildly symptomatic mother. No other maternal family members were available for testing. The present case of mitochondrial cytopathy initially presenting with steroid‐resistant nephrotic syndrome, unusual biochemical and renal findings associated with a novel tRNA point mutation suggests that steroid‐resistant FSGS can predate other features of mitochondrial disease for a prolonged period of time and that the progressive glomerulopathy associated with combined mitochondrial RC defects is genetically heterogeneous. © 2003 Wiley‐Liss, Inc.