title: Severe manifestation of Leber's hereditary optic neuropathy due to 11778G>A mtDNA mutation in a female with hypoestrogenism due to Perrault syndrome.
abstract: Perrault syndrome (PS) is a rare autosomal recessive condition with ovarian dysgenesis, hearing deficit and neurological abnormalities in female patients. The molecular basis of the syndrome is heterogeneous, mutations in the HSD17B4 gene have been identified in one family and mutations in the HARS2 gene have been found in another one. We have excluded pathogenic changes in the HSD17B4 gene and in the HARS2 gene by a direct sequencing of all coding exons in a female with clinical hallmarks of PS, ataxia and mild mental retardation. In addition, the patient suffers from severe Leber's hereditary optic neuropathy (LHON) due to 11778G>A mtDNA mutation. This case is the first reported patient with PS and LHON. Possible influence of hypoestrogenism on the manifestation of optic neuropathy in this patient is discussed in the context of recent findings concerning the crucial role of estrogens in supporting the vision capacity in LHON-related mtDNA mutation carriers.
authors.affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Sciences, Poznań, Poland; Center for Medical Genetics GENESIS, Poznań, Poland. Electronic address: bstronka@gmail.com.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Badura-Stronka
authors.forename: Anna
authors.initials: A
authors.lastname: Wawrocka
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zawieja
authors.forename: Sylwia
authors.initials: S
authors.lastname: Silska
authors.forename: Maciej Robert
authors.initials: MR
authors.lastname: Krawczyński
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D004967:Estrogens / Q000097:blood*; D005260:Female; D023961:Gonadal Dysgenesis, 46,XX / Q000473:pathology*; D006319:Hearing Loss, Sensorineural / Q000473:pathology*; D006801:Humans; D008297:Male; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000473:pathology*; D010375:Pedigree; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D004967:Estrogens
keywords: HARS2 gene; HSD17B4 gene; Hypoestrogenism; LHON; Perrault syndrome