The first two Chinese Myhre syndrome patients with the recurrent SMAD4 pathogenic variants: functional consequences and clinical diversity.

The first two Chinese Myhre syndrome patients with the recurrent SMAD4 pathogenic variants: functional consequences and clinical diversity. Clin Chim Acta. 2019 Oct 22;: Authors: Li H, Cheng B, Hu X, Li C, Su J, Zhang S, Li L, Li M, Yang K, He S, Chen S, Wang H, Liu G, Shen Y Abstract Myhre syndrome is a rare autosomal dominant multi-organ disorder characterized by growth retardation, skeletal anomalies, muscular hypertrophy, joint stiffness, facial dysmorphism, deafness, cardiovascular disease, and abnormal sexual development. Here we described the first two Chinese Myhre syndrome patients diagnosed by whole-exome sequencing. They both had de novo c.1498A>G (p.Ile500Val) variant in SMAD4 and presented with key characteristics of Myhre syndrome but also revealed uncommon features (polydactyly in the girl and precocious puberty in the boy). We performed functional analysis on four previously reported SMAD4 pathogenic variants in Myhre syndrome patients using dual-luciferase assay. Our results revealed that the pathogenic variants resulted in a variable degree of increased transcription activity of target genes that contain the minimal SMAD binding elements in their promoter regions. The boy responded to the recombinant human growth hormone treatment with improved height but also led to hyperinsulinemia and advanced bone age. Because of his precocious puberty, we subsequently combined the recombinant human growth hormone and gonadot...
Source: International Journal of Clinical Chemistry - Category: Chemistry Authors: Tags: Clin Chim Acta Source Type: research