Session: SUN 524-553-Male Reproductive Endocrinology
Bench to Bedside
Poster Board SUN-550
Patients and methods: Reviewing our cohort of 1,371 patients with IGD and 328 probands from identified from the published literature, 12 recurrent (i.e. occurring in ≥3 different families) mutations in 6 genes known to cause IGD (GNRHR, TACR3, PROKR2, FGFR1, KAL1, and HS6ST1) surfaced as candidates for founder genes. Using single nucleotide polymorphisms (SNPs) and microsatellite markers encompassing >3X recombination hotspots on either side of the mutation, we defined the haplotype of each and estimated their age according to haplotype size and haplotype decay model.
Results: Two mutations in GNRHR, p.R262Q and p.R139H, were found to share a common ancestral haplotype in Caucasian IGD patients. The estimated age of p.R262Q and p.R139H alleles was ~4,700 and 4,800 years, respectively.
Conclusions: GNRHR p.R262Q and p.R139H mutations are new founder mutations and join an expanding list of founder alleles associated with IGD. In contrast to the PROKR2 founder allele, both GNRHR mutations arose after the onset of human population expansion suggesting a weak purifying selection of these alleles without a heterozygote advantage to carriers. The precise heterozygote advantage of the PROKR2 founder mutation requires further investigation.
Nothing to Disclose: JHC, RB, LCP, CLB, YS, MLK, SW, ACL, CD, TO, LCL, JFG, WFC Jr.
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
See more of: Abstracts - Orals, Featured Poster Presentations, and Posters