Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced isoform

OBJECTIVE: To determine the prevalence of fibroblast growth factor receptor 1 (FGFR1) mutations and their predicted functional consequences in patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Cross-sectional study. SETTING: Multicentric. PATIENT(S): Fifty unrelated patients with IHH (21 with Kallmann syndrome and 29 with normosmic IHH). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patients were screened for mutations in FGFR1. The functional consequences of mutations were predicted by in silico structural and conservation analysis. RESULT(S): Heterozygous FGFR1 mutations were identified in six (12%) kindreds. These consisted of frameshift mutations (p.Pro33-Alafs*17 and p.Tyr654*) and missense mutations in the signal peptide (p.Trp4Cys), in the D1 extracellular domain (p.Ser96Cys) and in the cytoplasmic tyrosine kinase domain (p.Met719Val). A missense mutation was identified in the alternatively spliced exon 8A (p.Ala353Thr) that exclusively affects the D3 extracellular domain of FGFR1 isoform IIIb. Structure-based and sequence-based prediction methods and the absence of these variants in 200 normal controls were all consistent with a critical role for the mutations in the activity of the receptor. Oligogenic inheritance (FGFR1/CHD7/PROKR2) was found in one patient. CONCLUSION(S): Two FGFR1 isoforms, IIIb and IIIc, result from alternative splicing of exons 8A and 8B, respectively. Loss-of-function of isoform IIIc is a cause of IHH, whereas isoform IIIb is thought to be redundant. Ours is the first report of normosmic IHH associated with a mutation in the alternatively spliced exon 8A and suggests that this disorder can be caused by defects in either of the two alternatively spliced FGFR1 isoform

Growth and development dynamics in agronomic crops under environmental stress

Plants are exposed to different kinds of adverse environmental conditions during their life cycle that ablate their productivity. These environmental fluctuations have detrimental effects on the crops in terms of growth and development. Plants are highly susceptible to abiotic stresses including drought, salinity, high temperature, and increasing heavy metal concentration. The changing events related to climatic conditions are the signs of consternation for crops to maintain their productivity. Due to global warming, drought and high temperature are serious concerns regarding effective crop production. Salinity also adversely affects growth and productivity by disrupting normal physiology and biochemistry of plants. It causes osmotic disturbance, nutritional imbalance, malfunction of photosynthetic machinery, and oxidative stress. Rapid urbanization and industrialization are polluting the arable lands with heavy metals which not only affects crop productivity but also interferes with human health. In the modern era, heavy metals, like lead, cadmium, chromium, mercury, and copper are main environmental hazards, especially in regions of higher anthropogenic activity. Contamination of agricultural soils with heavy metals is a serious concern owing to its deleterious effects on agricultural productivity, phytotoxicity, food safety, and quality of the environment with ultimate impact on human health. All these abiotic stresses negatively affect several growth and developmental processes of plants which reduce the productivity of agronomic crop and also deteriorate the quality of produce. To cope with the situation, it is inevitable to understand the adverse effects of these abiotic factors on crop plants. This chapter provides comprehensive information on the impacts of abiotic stresses on crop plants