X chromosome inactivation does not define the development of premature ovarian failure in fragile X premutation carriers. 2010

Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.spath@obgyn.umcn.nl

Since only 20% of female fragile X premutation carriers develop premature ovarian failure (POF, i.e., amenorrhea before age of 40 years), and since X chromosome inactivation (XCI) determines the phenotypic severity of full mutation women, we reasoned that the development of POF in fragile X premutation carriers could be due to skewed XCI (XCI ratio >80:20). To determine inactivation ratios and activities of the premutations, inactivation patterns were assessed in peripheral blood samples from 101 fragile X premutation carriers (mean age 47.1 years, range 12-72) through analysis of the AR and FMR1 loci, respectively. In addition, AR inactivation patterns were assessed in peripheral blood samples from 25 women with idiopathic POF (mean age 31.7 years, range 19-48). We addressed the association between age and skewed XCI because older women are prone to XCI skewness. The median XCI ratios were 68% for premutation carriers with POF (N = 37), 67% for premutation carriers without POF (N = 64) and 61% for women with idiopathic POF (N = 25). The incidence of skewing was similar in all groups, that is, 7 of 37 (18.9%) in premutation carriers with POF, 11 of 64 (17.2%) in premutation carriers without POF, and 3 of 25 (12%) in women with idiopathic POF. There was good concordance between inactivation ratios at the two loci tested in 62 premutation carriers (intraclass correlation coefficient = 0.86; P < 0.01). No age-specific skewing was observed. Skewed XCI and activity of the premutation are not associated with POF in fragile X premutation carriers.

UI MeSH Term Description Entries
D007621 Karyotyping Mapping of the KARYOTYPE of a cell. Karyotype Analysis Methods,Analysis Method, Karyotype,Analysis Methods, Karyotype,Karyotype Analysis Method,Karyotypings,Method, Karyotype Analysis,Methods, Karyotype Analysis
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D005260 Female Females
D005600 Fragile X Syndrome A condition characterized genotypically by mutation of the distal end of the long arm of the X chromosome (at gene loci FRAXA or FRAXE) and phenotypically by cognitive impairment, hyperactivity, SEIZURES, language delay, and enlargement of the ears, head, and testes. INTELLECTUAL DISABILITY occurs in nearly all males and roughly 50% of females with the full mutation of FRAXA. (From Menkes, Textbook of Child Neurology, 5th ed, p226) FRAXA Syndrome,FRAXE Syndrome,Martin-Bell Syndrome,Fra(X) Syndrome,Fragile X Mental Retardation Syndrome,Fragile X-F Mental Retardation Syndrome,Mar (X) Syndrome,Marker X Syndrome,Mental Retardation, X-Linked, Associated With Fragile Site Fraxe,Mental Retardation, X-Linked, Associated With Marxq28,X-Linked Mental Retardation and Macroorchidism,FRAXA Syndromes,FRAXE Syndromes,Fragile X Syndromes,Marker X Syndromes,Martin Bell Syndrome,Syndrome, FRAXA,Syndrome, FRAXE,Syndrome, Fragile X,Syndrome, Marker X,Syndrome, Martin-Bell,Syndromes, FRAXA,Syndromes, FRAXE,Syndromes, Fragile X,Syndromes, Marker X,X Linked Mental Retardation and Macroorchidism
D006579 Heterozygote An individual having different alleles at one or more loci regarding a specific character. Carriers, Genetic,Genetic Carriers,Carrier, Genetic,Genetic Carrier,Heterozygotes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D015331 Cohort Studies Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. Birth Cohort Studies,Birth Cohort Study,Closed Cohort Studies,Cohort Analysis,Concurrent Studies,Historical Cohort Studies,Incidence Studies,Analysis, Cohort,Cohort Studies, Closed,Cohort Studies, Historical,Studies, Closed Cohort,Studies, Concurrent,Studies, Historical Cohort,Analyses, Cohort,Closed Cohort Study,Cohort Analyses,Cohort Studies, Birth,Cohort Study,Cohort Study, Birth,Cohort Study, Closed,Cohort Study, Historical,Concurrent Study,Historical Cohort Study,Incidence Study,Studies, Birth Cohort,Studies, Cohort,Studies, Incidence,Study, Birth Cohort,Study, Closed Cohort,Study, Cohort,Study, Concurrent,Study, Historical Cohort,Study, Incidence

Related Publications

Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
January 2009, Menopause (New York, N.Y.),
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
April 1999, American journal of medical genetics,
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
July 2000, American journal of human genetics,
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
July 2000, American journal of human genetics,
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
May 1998, Human reproduction (Oxford, England),
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
January 2008, South Dakota medicine : the journal of the South Dakota State Medical Association,
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
January 2000, Human reproduction (Oxford, England),
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
August 2003, Human reproduction (Oxford, England),
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
February 2004, European journal of obstetrics, gynecology, and reproductive biology,
Marian A Spath, and Willy N Nillesen, and Arie P T Smits, and Ton B Feuth, and Didi D M Braat, and Ad Geurts van Kessel, and Helger G Yntema
September 2004, The Journal of clinical endocrinology and metabolism,
Copied contents to your clipboard!