Localization of the human FSH receptor to chromosome 2 p21 using a genomic probe comprising exon 10

Gromoll, Jörg; Ried, Thomas; Holtgreve-Grez, H; Nieschlag, Eberhard; Gudermann, Thomas

doi:10.1677/jme.0.0120265

Cited by 59 publications

(26 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two additional candidate genes on chromosome 2 that could influence multiple ovulation and twinning frequency are the receptor for FSH (FSHR) and the ␤ B -inhibin subunit (IN-HBB). FSHR is located at 2p21-p16 (42,43), and INHBB is located at 2cen-q13 (39). The locations of both loci lie outside the small peak between D2S142 and D2S326.…”

Section: Discussionmentioning

confidence: 91%

Dizygotic Twinning Is Not Linked to Variation at the -Inhibin Locus on Human Chromosome 2

Montgomery¹

2000

Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

Natural multiple pregnancy in women leading to dizygotic (DZ) twins is familial and varies across racial groups, suggesting a genetic predisposition. Mothers of DZ twins have a higher incidence of spontaneous multiple ovulation and elevated FSH concentrations. FSH release is controlled by feedback of inhibin peptides from the ovary, and immunization against inhibin ␣-subunit results in an increased ovulation rate in animals. The inhibin ␣-subunit is therefore a candidate gene for mutations that may increase the frequency of DZ twinning. Restriction digests of a PCR product from exon 1 with the enzyme SpeI detects a C/T polymorphism at bp 128 with two alleles of 447 and 323/124 bp. The polymorphism was typed in 1125 individuals from 326 pedigrees with 717 mothers of spontaneous DZ twins. The ␣-inhibin locus mapped within 3 centimorgans of D2S164, and linkage with DZ twinning was excluded [decimal log odds ratio (LOD) score, Ϫ2.81 at ϭ 0]. There was complete exclusion of linkage (LOD, less than Ϫ2) of a gene conferring relative risk 1.8 (s, Ͼ1.8) across the chromosome, except at the p-terminus region and a small peak (maximum LOD score, 0.6) in the region of D2S151-D2S326. Analysis using either recessive or dominant models excluded linkage with DZ twinning in this population (LOD score, less than Ϫ2.5) across chromosome 2. We conclude that dizygotic twinning is not linked to variation in the ␣-inhibin locus. The results also suggest that mutations in other candidates on chromosome 2, including the receptor for FSH and the ␤ B -inhibin subunit (INHBB) cannot be major contributors to risk for DZ twinning. (J Clin Endocrinol Metab 85: 3391-3395, 2000) N ATURAL MULTIPLE pregnancy in women leading to dizygotic (DZ) twins is familial and varies across racial groups, suggesting a genetic predisposition. Female DZ twins and sisters of DZ twins have an increased frequency of twins compared with male DZ twins or brothers of DZ twins (1). Genetic effects on DZ twinning have been confirmed in subsequent investigations, but the estimated effects and modes of inheritance vary between studies (2-4). Analysis of families of 6596 twin pairs from the Australian Twin Registry found significantly higher frequencies of DZ twins in female relatives of DZ probands compared with MZ probands (4). The relative risks of DZ twin pregnancy for sisters of women with DZ twins and for female offspring of DZ probands were 1.7 and 2.5, respectively (4). Bulmer (2) postulated a recessive model of inheritance for DZ twinning, with a frequency of 0.5 and a penetrance of 5% in susceptible women, based on the data pooled from several studies. Segregation analysis of a Belgian/Dutch population-based study of twinning pedigrees suggests a dominant model of inheritance, with a gene frequency of 0.03 and a penetrance of 10% (3).DZ twinning results from the release and fertilization of multiple oocytes, and mothers of DZ twins have a higher incidence of spontaneous multiple follicle growth and multiple ovulation (5, 6). Several studies report in...

show abstract

Section: Discussionmentioning

confidence: 91%

Dizygotic Twinning Is Not Linked to Variation at the -Inhibin Locus on Human Chromosome 2

Montgomery¹

2000

Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

show abstract

“…The mean hospitalization period for these patients was 10.2G6.5 days. Sixteen patients were (Gromoll et al 1994). Gene map courtesy of National Center for Biotechnology Information http://www.ncbi.nlm.nih.gov.…”

Section: Distribution and Morbidity Of Ohss Patientsmentioning

confidence: 99%

Association of FSH receptor and CYP19A1 gene variations with sterility and ovarian hyperstimulation syndrome

Binder¹,

Dittrich²,

Hager³

et al. 2007

Reproduction

View full text Add to dashboard Cite

Severe ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication during assisted reproduction technology (ART). The aetiology of this condition is still not fully understood. Several gene variations in the FSH receptor (FSHR) gene have been identified for the very rare cases of spontaneous OHSS. There are only few published data on gene variations in sterility and iatrogenic OHSS and no data regarding aromatase (cytochrome P450 19A1; CYP19A1). Ninety-one ART patients with OHSS, eighty-eight ART patients without OHSS and ninety-seven women with assumed normal fecundity were analysed for the FSHR single nucleotide polymorphism (SNP) gene variations Asn680Ser (rs6166), Ala189Val, Ile160Thr, Thr449Ile (rs28928870) and the CYP19A1 rs10046 locus using real-time PCR. In addition, exon 10 of FSHR of two patients with spontaneous hyperreactio luteinalis (HL) was sequenced. Significantly lower frequencies of homozygous Ser

show abstract

“…The FSHR encoding gene was mapped to the short arm of chromosome 2 in 2p16.3. 3 It consists of 10 exons and spans about 54 kb of genomic DNA. 4 Mutations can be activating or inactivating.…”

Section: Introductionmentioning

confidence: 99%

An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance

et al. 2010

View full text Add to dashboard Cite

Follicle-stimulating hormone (FSH) mediated by its receptor (FSHR) is pivotal for normal gametogenesis. Inactivating FSHR mutations are known to cause hypergonadotropic hypogonadism with disturbed follicular maturation in females. So far, only very few recessive point mutations have been described. We report on a 17-year-old female with primary amenorrhea, hypergonadotropic hypogonadism and disturbed folliculogenesis. Chromosome analysis detected a seemingly balanced translocation 46,XX,t(2;8)(p16.3or21;p23.1)mat. FSHR sequence analysis revealed a novel non-synonymous point mutation in exon 10 (c.1760C4A, p.Pro587His), but no wild-type allele. The mutation was also found in the father, but not in the mother. Furthermore, molecular-cytogenetic analyses of the breakpoint region on chromosome 2 showed the translocation to be unbalanced, containing a deletion with one breakpoint within the FSHR gene. The deletion size was narrowed down by array analysis to approximately 163 kb, involving exons 9 and 10 of the FSHR gene. Functional studies of the mutation revealed the complete lack of signal transduction presumably caused by a changed conformational structure of transmembrane helix 6. To our knowledge, this is the first description of a compound heterozygosity of an inactivating FSHR point mutation unmasked by a partial deletion. This coincidence of two rare changes caused clinical signs consistent with FSH resistance.

show abstract

Localization of the human FSH receptor to chromosome 2 p21 using a genomic probe comprising exon 10

Cited by 59 publications

References 0 publications

Dizygotic Twinning Is Not Linked to Variation at the -Inhibin Locus on Human Chromosome 2

Dizygotic Twinning Is Not Linked to Variation at the -Inhibin Locus on Human Chromosome 2

Association of FSH receptor and CYP19A1 gene variations with sterility and ovarian hyperstimulation syndrome

An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance

Contact Info

Product

Resources

About