Clinical trial NCT01177891: Genetic Analysis of Familial Cases of Premature Ovarian Failure
Official title: Genetic Analysis of Familial Cases of Premature Ovarian Failure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Familial Premature Ovarian Failure
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2010-08-09
Enrollment: 110
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Caucasian population

Brief summary: The Premature ovarian failure (POF) is a rare syndrome observed in women under 40 who induced estrogen deficiency and often leads to infertility final. The etiologies of POF remain unknown in more than 85% of cases. There are 5-10 % of familial cases.The main objective of this study is to recruit, phenotype and genotype 20 families with at least two subjects with nonsyndromic POF in order to identify new loci using a single technical standard nucleotide polymorphisms (SNPs). This study will also include related population and population control.

Detailed description: It was decided to move towards a study of familial cases of IOP. This study will identify areas of susceptibility in new families, identify candidate genes, sequence these genes in cases familial POF and sporadic cases in order to detect potential mutations, and in the control population.

Eligibility criteria: Inclusion Criteria:

Patients of familial cases of POF :

* Female subjects between 16 and 40 years or women older than 40 years with a cessation of ovarian function before the age of 40 years with increased levels of FSH
* Primary or secondary amenorrhea for more than three months with LH and FSH\> 30mUI/ml
* No cases of fragile X syndrome in the family or blepharophimosis syndrome
* At least two cases in the family
* Origin Caucasian
* Patient signing the consent form for at least the blood sample
* Patient with Social Security

Population Index related topics :

* The presence of cycles until the age of 40 years with proven fertility, at least one child
* Amenorrhea and FSH\> 30mUI/ml according to the criteria of the index subject
* Men of the family of index case

Population control :

* Women of Caucasian origin
* Women who had regular cycles until at least age 40 and at least one child
* Lack of land autoimmune (no history of thyroid disease or diabetes type 1)
* Woman signing the consent form for at least the blood sample

Exclusion Criteria:

* Blood donation of more than 450ml in the previous three months.
* Subject with an abnormal karyotype in favor of Turner syndrome or having a premutation of the FMR1 gene or a syndromic form
* Subject exclusion period in another study without direct individual benefit
* Subject refusing to sign the consent form

Primary outcomes:
measure: Identification of candidate regions by genotyping within families
timeFrame: 1 day
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Hospital Saint-Antoine, Endocrinology service
city: Paris
country: France
facility: Sophie Christin-Maitre
Study officials:
affiliation: Saint-Antoine hospital, Service of Endocrinology, ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
name: Sophie Christin-Maitre, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Charbit B, Christin-Maitre S, Demolis JL, Soustre E, Young J, Funck-Brentano C. Effects of testosterone on ventricular repolarization in hypogonadic men. Am J Cardiol. 2009 Mar 15;103(6):887-90. doi: 10.1016/j.amjcard.2008.11.041. Epub 2009 Jan 24.
citation: Rousseau A, Ayoubi F, Deveaux C, Charbit B, Delmau C, Christin-Maitre S, Jaillon P, Uzan G, Simon T. Impact of age and gender interaction on circulating endothelial progenitor cells in healthy subjects. Fertil Steril. 2010 Feb;93(3):843-6. doi: 10.1016/j.fertnstert.2008.10.062. Epub 2008 Dec 25.
citation: Warcoin M, Lespinasse J, Despouy G, Dubois d'Enghien C, Lauge A, Portnoi MF, Christin-Maitre S, Stoppa-Lyonnet D, Stern MH. Fertility defects revealing germline biallelic nonsense NBN mutations. Hum Mutat. 2009 Mar;30(3):424-30. doi: 10.1002/humu.20904.
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citation: Beysen D, De Jaegere S, Amor D, Bouchard P, Christin-Maitre S, Fellous M, Touraine P, Grix AW, Hennekam R, Meire F, Oyen N, Wilson LC, Barel D, Clayton-Smith J, de Ravel T, Decock C, Delbeke P, Ensenauer R, Ebinger F, Gillessen-Kaesbach G, Hendriks Y, Kimonis V, Laframboise R, Laissue P, Leppig K, Leroy BP, Miller DT, Mowat D, Neumann L, Plomp A, Van Regemorter N, Wieczorek D, Veitia RA, De Paepe A, De Baere E. Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome. Hum Mutat. 2008 Nov;29(11):E205-19. doi: 10.1002/humu.20819.
citation: Chakhtoura Z, Bachelot A, Samara-Boustani D, Ruiz JC, Donadille B, Dulon J, Christin-Maitre S, Bouvattier C, Raux-Demay MC, Bouchard P, Carel JC, Leger J, Kuttenn F, Polak M, Touraine P; Centre des Maladies Endocriniennes Rares de la Croissance and Association Surrenales. Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency. Eur J Endocrinol. 2008 Jun;158(6):879-87. doi: 10.1530/EJE-07-0887. Epub 2008 Apr 7.
citation: Christin-Maitre S. [Physiology of ovulation and mode of action of contraceptive pills]. Rev Prat. 2008 Jan 15;58(1):17-20. French.
citation: Christin-Maitre S. The role of hormone replacement therapy in the management of premature ovarian failure. Nat Clin Pract Endocrinol Metab. 2008 Feb;4(2):60-1. doi: 10.1038/ncpendmet0699. Epub 2007 Nov 20. No abstract available.
citation: Tachdjian G, Aboura A, Portnoi MF, Pasquier M, Bourcigaux N, Simon T, Rousseau G, Finkel L, Benkhalifa M, Christin-Maitre S. Cryptic Xp duplication including the SHOX gene in a woman with 46,X, del(X)(q21.31) and premature ovarian failure. Hum Reprod. 2008 Jan;23(1):222-6. doi: 10.1093/humrep/dem358. Epub 2007 Nov 1.
citation: Vinci G, Christin-Maitre S, Pasquier M, Bouchard P, Fellous M, Veitia RA. FOXO3a variants in patients with premature ovarian failure. Clin Endocrinol (Oxf). 2008 Mar;68(3):495-7. doi: 10.1111/j.1365-2265.2007.03052.x. Epub 2007 Sep 19. No abstract available.
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citation: Roux C, Briot K, Dumarcet N, Bourgoin M, Chapurlat R, Christin-Maitre S, Cortet B, Costagliola D, Diebolt V, Lacoin F, Letombe B, Oberlin F, Orcel P, Ravaud P, Seret P, Thomas T, Vogel JY, Barna A, Nouyrigat E, Veyries ML, Yoldjian I. [Drug treatment of postmenopausal osteoporosis. What's New in 2006]. Presse Med. 2006 Oct;35(10 Pt 2):1529-39. doi: 10.1016/s0755-4982(06)74847-3. No abstract available. French.
citation: Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, Aittomaki K, Bourcigaux N, Jacquesson L, Bouchard P, Frydman R, Dewailly D, Reyss AC, Jeffery L, Bachelot A, Massin N, Fellous M, Veitia RA. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol. 2006 May;154(5):739-44. doi: 10.1530/eje.1.02135.
citation: De Baere E, Copelli S, Caburet S, Laissue P, Beysen D, Christin-Maitre S, Bouchard P, Veitia R, Fellous M. Premature ovarian failure and forkhead transcription factor FOXL2: blepharophimosis-ptosis-epicanthus inversus syndrome and ovarian dysfunction. Pediatr Endocrinol Rev. 2005 Jun;2(4):653-60.
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citation: Ouzounian S, Christin-Maitre S. [What is menopause?]. Rev Prat. 2005 Feb 28;55(4):363-8. French.
citation: Simon T, Boutouyrie P, Gompel A, Christin-Maitre S, Laurent S, Thuillez C, Zannad F, Bernaud C, Jaillon P; CASHMERE investigators. Rationale, design and methods of the CASHMERE study. Fundam Clin Pharmacol. 2004 Feb;18(1):131-8. doi: 10.1111/j.1472-8206.2003.00233.x.
citation: Hulot JS, Demolis JL, Riviere R, Strabach S, Christin-Maitre S, Funck-Brentano C. Influence of endogenous oestrogens on QT interval duration. Eur Heart J. 2003 Sep;24(18):1663-7. doi: 10.1016/s0195-668x(03)00436-6.
citation: Christin-Maitre S, Ronci-Chaix N, Bouchard P. [Ovary genes and molecular pathology]. J Soc Biol. 2002;196(3):207-16. French.
citation: Rouen A, Rogers E, Kerlan V, Delemer B, Catteau-Jonard S, Reznik Y, Gompel A, Cedrin I, Guedj AM, Grouthier V, Brue T, Pienkowski C, Bachelot A, Chantot-Bastaraud S, Rousseau A, Simon T, Kott E, Siffroi JP, Touraine P, Christin-Maitre S. Whole exome sequencing in a cohort of familial premature ovarian insufficiency cases reveals a broad array of pathogenic or likely pathogenic variants in 50% of families. Fertil Steril. 2022 Apr;117(4):843-853. doi: 10.1016/j.fertnstert.2021.12.023. Epub 2022 Jan 31.