title: Mitochondrial DNA mutations in a patient with sex reversal and clinical features consistent with Fraser syndrome.
abstract: We describe a 20-year-old 46,XY woman, with clinical findings of Fraser syndrome and three mitochondrial DNA (mtDNA) mutations of Leber hereditary optic neuropathy. The patient had microphthalmia, blindness, widely spaced nipples, bifid ureter, syndactyly of the toes, and mental retardation. Sonography showed the presence of a uterus and intra-abdominal gonads. The proband was screened for mtDNA mutations because of chronic gastrointestinal pseudo-obstruction, urinary tract dysmotility, seizures, mental retardation and persistent macrocytosis, as well as the intermittent elevation of methylmalonic acid. Analysis of point mutations by multiplex polymerase chain reaction and allele-specific oligonucleotide dot-blot hybridization revealed three homoplasmic mtDNA mutations, T14484C, T4216C, and T3394C. This represents a unique case with sex reversal, Fraser-like syndrome, and mitochondrial disease.
authors.affiliation: Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DC 20007, USA. wonglj@georgetown.edu
authors.forename: L-J C
authors.initials: LJ
authors.lastname: Wong
authors.forename: Y-H
authors.initials: YH
authors.lastname: Lin
authors.forename: P
authors.initials: P
authors.lastname: Suwannarat
authors.forename: C-H
authors.initials: CH
authors.lastname: Hsu
authors.forename: H-Y
authors.initials: HY
authors.lastname: Kwon
authors.forename: S
authors.initials: S
authors.lastname: Mackowiak
mesh_terms: D000015:Abnormalities, Multiple; D000328:Adult; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial; D030321:Denys-Drash Syndrome / Q000235:genetics* / Q000473:pathology; D012734:Disorders of Sex Development; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial; D016326:Extracellular Matrix Proteins; C475145:FRAS1 protein, human