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| Name | Class |
|---|---|
| Swiss National Science Foundation | OTHER |
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The purpose of this study is to explore the genetic basis of reproductive disorders and cleft lip and/or palate.
The World Health Organization estimates approximately 10% of couples experience some sort of infertility problem.
In humans, puberty is the process through which we develop reproductive capacity.
The timing of puberty varies greatly in the general population and is influenced by both genetic and environmental factors. In extreme cases of pubertal delay, puberty progresses only partially or not at all and results in the clinical picture of congenital hypogonadotropic hypogonadism (CHH), either accompanied by anosmia in 50% of cases (Kallmann syndrome [KS]) or by normal sense of smell (nCHH), with a male: female ratio of 4:1.
CHH is due to GnRH deficiency (incidence 1: 4,000-10,000) and result in the failure of sexual maturation and infertility. It is genetically heterogeneous, with multiple patterns of inheritance and several associated loci. In the clinical spectrum of GnRH deficiency, CHH may also be associated with a cleft lip/palate (CL/P) in 5 to 7% of cases. However, this prevalence increases up to 40% in CHH patients carrying a mutation in a CL/P gene, suggesting a genetic overlap between CHH and CL/P.
Disorders of puberty have provided insight into the biology of reproduction and genetic technologies have enabled us to deepen understanding in this field. The focus of this study is to better understand the genetic control of puberty and human reproduction as well as its link with CL/P.
Increasing understanding of the molecular basis (genes) of inherited reproductive disorders and CL/P may enable investigators to:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients | Patients with reproductive disorders with or without cleft lip/palate will be recruited for:
| ||
| Family members | Family members of Patients will be recruited for:
|
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| Measure | Description | Time Frame |
|---|---|---|
| rare sequence variant(s) in gene(s) | The investigators aim to discover genes associated with reproductive disorders by identifying rare sequence variants (mutations) in patients | 1 year (ongoing if no variants are identified) |
| Measure | Description | Time Frame |
|---|---|---|
| functionality of identified rare sequence variants (mutations) | The investigators will use a variety of scientific approaches to assess the functional impact of the identified rare sequence variants (mutations) | 1 year (following variant identification) |
| mode of inheritance |
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Inclusion Criteria:(any of the following conditions)
Exclusion Criteria:
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Study participants will be a convenience sample of those patients with reproductive disorders (and their family members), with or without cleft lip/palate, who are interested in participating in this genetic study.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Emmanuelle Paccou | Contact | +41 79 556 60 13 | emmanuelle.paccou@chuv.ch | |
| Michela Adamo, MD | Contact | +41 079 556 85 14 | michela.adamo@chuv.ch |
| Name | Affiliation | Role |
|---|---|---|
| Nelly Pitteloud, M.D. | Centre Hositalier Universitaire Vaudois (CHUV) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire Vaudois (CHUV) | Recruiting | Lausanne | Canton of Vaud | 1011 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23643382 | Result | Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008. | |
| 25394172 |
| Label | URL |
|---|---|
| Web page for the Principal Investigator Nelly Pitteloud's research group | View source |
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whole blood, serum/plasma, white blood cells, DNA
The investigators will examine family pedigrees and study family members to determine the inheritance patterns (how the disorder is transmitted in the family) |
| 1 year (following variant identification) |
| genotype-phenotype correlation | The investigators will study the phenotypic spectrum (how the disorder presents clinically) in patients with identified rare sequence variants (mutations) | 1 year (following variant identification) |
| Result |
| Villanueva C, Jacobson-Dickman E, Xu C, Manouvrier S, Dwyer AA, Sykiotis GP, Beenken A, Liu Y, Tommiska J, Hu Y, Tiosano D, Gerard M, Leger J, Drouin-Garraud V, Lefebvre H, Polak M, Carel JC, Phan-Hug F, Hauschild M, Plummer L, Rey JP, Raivio T, Bouloux P, Sidis Y, Mohammadi M, de Roux N, Pitteloud N. Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations. Genet Med. 2015 Aug;17(8):651-9. doi: 10.1038/gim.2014.166. Epub 2014 Nov 13. |
| ID | Term |
|---|---|
| D017436 | Kallmann Syndrome |
| D007006 | Hypogonadism |
| D011085 | Polycystic Ovary Syndrome |
| D011629 | Puberty, Precocious |
| D002971 | Cleft Lip |
| D002972 | Cleft Palate |
| D000086582 | Anosmia |
| D007246 | Infertility |
| D003456 | Cryptorchidism |
| C536649 | Penis agenesis |
| ID | Term |
|---|---|
| D058490 | Disorder of Sex Development, 46,XY |
| D012734 | Disorders of Sex Development |
| D014564 | Urogenital Abnormalities |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D000091662 | Genital Diseases |
| D008047 | Lip Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D009056 | Mouth Abnormalities |
| D018640 | Stomatognathic System Abnormalities |
| D007569 | Jaw Abnormalities |
| D007571 | Jaw Diseases |
| D009140 | Musculoskeletal Diseases |
| D019767 | Maxillofacial Abnormalities |
| D019465 | Craniofacial Abnormalities |
| D009139 | Musculoskeletal Abnormalities |
| D000857 | Olfaction Disorders |
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D013733 | Testicular Diseases |
| D005832 | Genital Diseases, Male |
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