A 9-year-old girl presented with lethargy, malaise & chest pain. Her blood counts confirmed hypochromic microcytic anemia. She was prescribed iron supplements. Subsequently she was admitted to our hospital with fever and increasing chest and abdominal pain. She was treated with antibiotics, and a diagnosis of "early chest infection" was made. Over the following 2 weeks she failed to improve, and her anemia worsened. She was readmitted, and found to have a mass in her lower abdomen with pressure symptoms on her bowel and bladder. A white-cell scan showed increased uptake in right lower quadrant. An ultrasound and a CT scan confirmed a mass adjacent to her bladder. Needle biopsy showed it to be an unusual localization of an inflammatory myofibroblastic tumor (IMT) of cecum. A presentation with chest pain, fever, anemia and pressure symptoms was highly unusual of a lower abdominal IMT mass. She had a successful excision of the tumor, with resolution of her symptoms.

Cystic fibrosis (CF) arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in progressive and life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterised. Our aims were to describe the clinical and molecular phenotypes associated with R751L. Relevant clinical data were collected from three heterozygote individuals harbouring R751L (2 patients with G551D/R751L and 1 with F508del/R751L). Assessment of R751L-CFTR function was made in primary human bronchial epithelial cultures (HBEs) and Xenopus oocytes. Molecular properties of R751L-CFTR were investigated in the presence of known CFTR modulators. Although sweat chloride was elevated in all three patients, the clinical phenotype associated with R751L was mild. Chloride secretion in F508del/R751L HBEs was reduced compared to non-CF HBEs and associated with a reduction in sodium absorption by the epithelial sodium channel (ENaC). However, R751L-CFTR function in Xenopus oocytes together with folding and cell surface transport of R751L-CFTR were not different to wild-type CFTR. Overall, R751L-CFTR was associated with reduced sodium chloride absorption but had similar functional properties to wild-type CFTR. This is the first report of R751L-CFTR that combines clinical phenotype with characterisation of functional and biological properties of the mutant channel. Our work will build upon existing knowledge of mutations within this region of CFTR and importantly inform approaches for clinical management. Elevated sweat chloride and reduced chloride secretion in HBEs may be due to alternative non-CFTR factors, which require further investigation.

The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis

No abstract