Variants of the BMP15 gene in a cohort of patients with premature ovarian failure.

BACKGROUND: Bone morphogenetic protein 15 (BMP15) is an oocyte-derived growth factor acting as a major player in follicle differentiation in mammals. Mutations in the BMP15 gene, some of which lead to defective secretion of bioactive dimers, have been associated with premature ovarian failure (POF) in humans. METHODS: Fifty patients diagnosed with POF with a normal karyotype were included in the study. After DNA extraction and amplification by PCR, the entire coding sequence and intron-exon junctions of BMP15 gene were analysed in the cohort of POF patients and in a control group of 214 patients. RESULTS: Nine variants of the BMP15 gene including six missense substitutions and one insertion of three nucleotides were identified in the POF group. Three of them were previously described as single nucleotide polymorphisms and were also found in the control group. Two variants (H81R and G199R) have not been previously described and were not identified among controls but were not predicted to be deleterious. One variant (A180T) was identified among two POF cases, and also in two controls. One variant (F194S), predicted as potentially deleterious, was identified for the first time in a POF patient but also identified in one control. One variant (L148P), potentially deleterious, previously reported in POF patients, was identified for the first time among controls. The variant 788insTCT, previously identified among POF patients, probably has a low biological impact as it was also found in control patients and is a common polymorphism in sub-Saharan African populations. CONCLUSIONS: Various missense variants of the BMP15 gene were identified among patients with POF. For most variants, the impact of the amino-acid substitution on the protein structure and function was predicted to be low. The two variants predicted as potentially deleterious were also identified among controls and could be considered as rare polymorphisms. Although some of these variants could contribute to the development of POF in a complex manner, the demonstration of their role in the pathogenesis of POF requires additional functional studies.

[The distribution and polymorphism of beta-2-adrenoreceptors in the bronchi]. / Distributia si polimorfismul receptorilor beta 2 adrenergici la nivel bronsic.

Genic variability has a role in bronchial asthma susceptibility and the influence of its gravity, and also influences therapy efficacy. Clinical trials demonstrated that beta2 adrenoreceptors variability has an influence on the response to bronchodilator therapy. Some mutations induce resistance to bronchial asthma occurrence (Q27E which reduces down-regulation), others make subjects susceptible to asthma (D79N, T1641 and most of all R16G by an intensive down-regulation), and a third kind of mutations has no influence whatsoever on this disease (1159L, 1159F, K375R). A better understanding of the molecular processes involved in different pathways in asthma can lead to pathophysiological details, to find a more efficient treatment.