A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome leading to a dramatically reduced biological function.

ABSTRACT:

Background

The Holt-Oram syndrome (HOS) is an autosomal dominant disorder affecting 1/100.000 live births. It is defined by upper limb anomalies and congenital heart defects with variable severity. We describe a dramatic phenotype of a male, 15-month-old patient being investigated for strict diagnostic criteria of HOS.

Methods and results

Genetic analysis revealed a so far unpublished TBX5 mutation, which occurs de novo in the patient with healthy parents. TBX5 belongs to the large family of T-box transcription factors playing major roles in morphogenesis and cell-type specification. The mutation located in the DNA-binding domain at position 920 (C→A) leads to an amino acid change at position 85 (proline → threonine). Three-dimensional analysis of the protein structure predi

SUBMITTER: Dreßen M 

PROVIDER: S-EPMC5023941 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature