S737F is a new CFTR mutation typical of patients originally from the Tuscany region in Italy

Background An increasing number of patients have been described as having a number of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) variants for which it lacks a clear genotype-phenotype correlation. We assesses the clinical features of patients bearing the S737F (p.Ser737Phe) CFTR missense variant and evaluated the residual function of CFTR protein on nasal epithelial cells (NEC). Methods A retrospective database was performed from individuals homozygous or compound heterozygous for the S737F variant followed in the Cystic Fibrosis (CF) Centre of Florence. We performed a nasal brushing in cooperating patients and compared the results with those of patients followed in the pediatric CF Centre of Naples. Results 9/295 (3%) subjects carrying at least S737F CFTR variant on one allele were identified. Patients were diagnosed in 7/9 cases by newborn screening and in two cases for dehydration with hypochloremic metabolic alkalosis; at diagnosis sweat chloride levels (SCL) were in the pathological range in only one case. After a mean follow up of 8,6 years (range 0,5-15,8), SCL were in the pathological range in 8/9 cases (mean age at CF diagnosis: 1,5 years), all patients were pancreatic sufficiency and respiratory function was normal. The gating activity on NEC was 15.6% and 12.7% in two patients compound heterozygous for W1282X and DelE22-24, while it was ranged between 6,2% and 9,8% in CF patients. Conclusions S737F is a CFTR mutation associated to hypochloremic alkalosis in childhood, mild CF phenotype in teenage years and a residual function of CFTR protein

Worsening of Cardiomyopathy Using Deflazacort in an Animal Model Rescued by Gene Therapy

We have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster. In patients with similar genetic defects, steroids have been largely used to slow down disease progression. Aim of our study was to evaluate the combined effects of steroid treatment and gene therapy on cardiac function. We injected the human delta-sarcoglycan cDNA by adeno-associated virus (AAV) 2/8 by a single intraperitoneal injection into BIO14.6 Syrian hamsters at ten days of age to rescue the phenotype. We then treated the hamsters with deflazacort. Treatment was administered to half of the hamsters that had received the AAV and the other hamsters without AAV, as well as to normal hamsters. Both horizontal and vertical activities were greatly enhanced by deflazacort in all groups. As in previous experiments, the AAV treatment alone was able to preserve the ejection fraction (70±7% EF). However, the EF value declined (52±14%) with a combination of AAV and deflazacort. This was similar with all the other groups of affected animals. We confirm that gene therapy improves cardiac function in the BIO14.6 hamsters. Our results suggest that deflazacort is ineffective and may also have a negative impact on the cardiomyopathy rescue, possibly by boosting motor activity. This is unexpected and may have significance in terms of the lifestyle recommendations for patients

Infarto estriatocapsular na infância: relato de quatro casos

Os autores apresentam o estudo de quatro crianças que manifestaram hemiparesia desproporcionada de instalação súbita, sem perda da consciência. O diagnóstico de infarto estriatocapsular foi confirmado pela tomografia computadorizada do crânio (TCC) e ressonância magnética (RM). Discutem os achados clínico-neurológicos e de exames complementares. História familiar de migrânea foi relatada em dois dos pacientes. Constatou-se migrânea em dois, trauma craniano, miocardite e prolapso de válvula mitral em um. Hemiparesia esquerda, com predomínio bráquio-facial em três e braquial em um. A TCC demonstrou comprometimento do núcleo lenticular e da cápsula interna nos quatro casos; da cabeça do núcleo caudado em três e da substância branca em dois. A RM foi realizada em dois e confirmou os achados da TCC. O eletrencefalograma, obtido na fase aguda em três, se mostrou alterado nos quatro casos