The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs.

Loss-of-function mutations of the gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination.

Variants in the 5'UTR reduce SHOX expression and contribute to SHOX haploinsufficiency.

SHOX haploinsufficiency causes 70-90% of Léri-Weill dyschondrosteosis (LWD) and 2-10% of idiopathic short stature (ISS). Deletions removing the entire gene or enhancers and point mutations in the coding region represent a well-established cause of haploinsufficiency. During diagnostic genetic testing on ISS/LWD patients, in addition to classic SHOX defects, five 5'UTR variants (c.

Skeletal dysplasia with bowing long bones: Proposed flowchart for prenatal diagnosis with case demonstration.

Objective: Skeletal dysplasia with bowing long bones is a rare group of multiple characterized congenital anomalies.

Materials And Methods: We introduce a simple, practical diagnostic flowchart that may be helpful in identifying the appropriate pathway of obstetrical management.

Results: Herein, we describe four fetal cases of bent bony dysplasia that focus on ultrasound findings, phenotype, molecular tests, distinctive X-ray features, and chondral growth plate histology.

Majewski syndrome (short-rib polydactyly syndrome type II): Prenatal diagnosis and histological features of chondral growth plate, liver and kidneys.

The Majewski syndrome or short rib-polydactyly syndrome (SRPS) type II is a lethal skeletal dysplasia characterized by severe IUGR (intrauterine growth restriction) and dysmorphic face, polydactyly, relatively proportionate head size at birth with later progression to microcephaly. A case of second trimester ultrasound diagnosis of SRPS type II is reported with review of the medical record of previous observed cases. Postmortem examination and radiogram confirmed the clinical diagnosis.