Two frequent loss-of-function mutations in Aurora Kinase C gene in Algerian infertile men with macrozoospermia.

Macrozoospermia is associated with severe male infertility. To date, the only gene implicated in this phenotype is the Aurora Kinase C gene. We report in this work the genetic screening of AURKC mutations in 34 patients with macrozoospermia among 3,536 Algerian infertile men.

DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

Background And Aims: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients is associated with worse long-term pulmonary disease and shorter survival, and chronic Pa infection (CPA) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in CF, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre.

CFTR and/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients?

Background/objectives: Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown.

Methods: Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded.

The p.Gly622Asp (G622D) mutation, frequently found in Reunion Island and in black populations, is associated with a wide spectrum of CF and CFTR-RD phenotypes.

Examination of genotype-phenotype correlations along with functional evaluation of CFTR mutations may not be straightforward. The c.1865G>A, p.

p.Arg75Gln, a CFTR variant involved in the risk of CFTR-related disorders?

c.224G>A, p.Arg75Gln (R75Q) presumably leads to an amino-acid change from arginine to glutamine in the membrane-spanning domain of the CFTR protein.

Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia.

The cystic fibrosis transmembrane conductance regulator (CFTR) is present in mature sperm and is required for sperm motility and capacitation. Both these processes are controlled by ions fluxes and are essential for fertilization. We have shown that SLC26A8, a sperm-specific member of the SLC26 family of anion exchangers, associates with the CFTR channel and strongly stimulates its activity.