Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7.

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Somatic variants in TRAF7 are linked to meningioma.
• Germline variants in TRAF7 have been associated with developmental delay and congenital anomalies.

Purpose of the Study:

• To characterize the clinical and mutational spectrum of TRAF7 germline variants.
• To investigate the molecular effects of TRAF7 variants using transcriptomic analysis.

Main Methods:

• Exome, targeted capture, and Sanger sequencing were used to identify TRAF7 variants in patients with developmental disorders.
• Whole-transcriptome sequencing of patient and control fibroblasts was performed.

Main Results:

• Heterozygous missense variants in TRAF7 were identified in 45 patients with a developmental delay-malformation syndrome.
• Key features include blepharophimosis, short neck, pectus carinatum, digital deviations, and patent ductus arteriosus.
• Most variants occurred in the WD40 repeats, and several differentially expressed genes were found in patient fibroblasts.

Conclusions:

• This study presents the largest analysis of the TRAF7 developmental syndrome to date.
• It elucidates the clinical presentation, genetic variations, and molecular underpinnings of the disorder.