POLG mutations and age at menopause.

نویسندگان

  • Andrew J Duncan
  • Jack A Knight
  • Harry Costello
  • Gerard S Conway
  • Shamima Rahman
چکیده

Bennett CE, Conway GS, Macpherson JN, Jacobs PA, Murray A. Intermediate sized CGG repeats are not a common cause of idiopathic premature ovarian failure. Hum Reprod 2010;25:1335–1338. Chen LS, Tassone F, Sahota P, Hagerman PJ. The (CGG)n repeat element within the 5′ untranslated region of the FMR1 message provides both positive and negative cis effects on in vivo translation of a downstream reporter. Hum Mol Genet 2003;12:3067–3074. Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJ, Holden JJ, Fenwick RG Jr, Warren ST et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 1991;67:1047–1058. Gleicher N, Weghofer A, Oktay K, Barad D. Relevance of triple CGG repeats in the FMR1 gene to ovarian reserve. Reprod Biomed Online 2009a;19:385–390. Gleicher N, Weghofer A, Oktay K, Barad DH. Can the FMR1 (fragile X) gene serve as predictor of response to ovarian stimulation? Reprod Sci 2009b;16:462–467. Gleicher N, Weghofer A, Oktay K, Barad DH. Correlation of triple repeats on the FMR1 (fragile X) gene to ovarian reserve: a new infertility test? Acta Obstet Gynecol Scand 2009c;88:1024–1030. Gleicher N, Weghofer A, Barad DH. Ovarian reserve determinations suggest new function of FMR1 (fragile X gene) in regulating ovarian ageing. Reprod Biomed Online 2010;20:768–775. Streuli I, Fraisse T, Ibecheole V, Moix I, Morris MA, de Ziegler D. Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency. Fertil Steril 2009;92:464–470.

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Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma.

BACKGROUND Premature ovarian failure (POF) results in menopause before the age of 40. Recently, mutations in the catalytic subunit of mitochondrial DNA polymerase gamma (POLG) were shown to segregate with POF in families with progressive external ophthalmoplegia (PEO) and multiple large-scale rearrangements of mitochondrial DNA (mtDNA). METHODS AND RESULTS A patient, mother and maternal grand...

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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

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Heterozygous Polg mutation causes motor dysfunction due to mtDNA deletions

OBJECTIVE Mutations in nuclear-encoded mitochondrial DNA (mtDNA) polymerase (POLG) are known to cause autosomal dominant chronic progressive external ophthalmoplegia (adCPEO) with accumulation of multiple mtDNA deletions in muscles. However, no animal model with a heterozygous Polg mutation representing mtDNA impairment and symptoms of CPEO has been established. To understand the pathogenic mec...

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Pathogenicity in POLG syndromes: DNA polymerase gamma pathogenicity prediction server and database

DNA polymerase gamma (POLG) is the replicative polymerase responsible for maintaining mitochondrial DNA (mtDNA). Disorders related to its functionality are a major cause of mitochondrial disease. The clinical spectrum of POLG syndromes includes Alpers-Huttenlocher syndrome (AHS), childhood myocerebrohepatopathy spectrum (MCHS), myoclonic epilepsy myopathy sensory ataxia (MEMSA), the ataxia neur...

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Polg and Other Mitochondrial Disease Relevance for Psychiatry

ver the last decade, novel mitochondrial genetic diseases have been identified in which mutations in DNA polymerase γ (POLG [MIM 174763]) gene are involved. POLG1 is the only DNA polymerase in human mitochondria and is essential for mitochondrial (mt) DNA replication and repair. It has to be stressed that functional genetic variants of POLG are present in about 0.5 percent of the normal populat...

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Role of Polymerase Gamma Mutations in Breast Tumorigenesis PRINCIPAL INVESTIGATOR:

Decreased mitochondrial oxidative phosphorylation (OXPHOS) is one of the hallmarks of cancer. To date the identity of nuclear gene(s) responsible for decreased OXPHOS in tumors remains unknown. It is also unclear whether mutations in nuclear gene(s) responsible for decreased OXPHOS affect tumorigenesis. Polymerase γ (POLG) is the only DNA polymerase known to function in human mitochondria. Muta...

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عنوان ژورنال:
  • Human reproduction

دوره 27 7  شماره 

صفحات  -

تاریخ انتشار 2012