Mitral Transcatheter Edge-to-Edge Repair in INTERMACS 3-4 Profile Patients with Severe Mitral Regurgitation.

Background: Heart transplantation and left ventricular assist device (LVAD) implementation are effective treatments for advanced heart failure (HF), although their use is limited by organ availability and the high incidence of adverse events. The efficacy of mitral transcatheter edge-to-edge repair (TEER) as a bridge to transplantation or as a destination therapy in advanced HF is still debated.

Methods: A total of 63 patients with INTERMACS class 3 or 4 with contraindications for LVAD and severe functional mitral regurgitation (FMR) were evaluated for TEER implantation eligibility.

A specific serum lipid signature characterizes patients with glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls.

Heterozygosity for loss-of-function variants in LZTR1 is associated with isolated multiple café-au-lait macules.

Purpose: Pathogenic LZTR1 variants cause schwannomatosis and dominant/recessive Noonan syndrome (NS). We aim to establish an association between heterozygous loss-of-function LZTR1 alleles and isolated multiple café-au-lait macules (CaLMs).

Methods: A total of 849 unrelated participants with multiple CaLMs, lacking pathogenic/likely pathogenic NF1 and SPRED1 variants, underwent RASopathy gene panel sequencing.

SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.

While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These "selfish" mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father's age, and high apparent germline mutation rate. To date, all known selfish mutations cluster within the components of the RTK-RAS-MAPK signaling pathway, a critical modulator of testicular homeostasis.