Non-Coding c.*6C>T Variant in RBM8A Associated With Thrombocytopenia-Absent Radius (TAR) Syndrome in Three Indian...

Area of Science:

• Genetics
• Molecular Biology
• Hematology

Background:

• Thrombocytopenia-absent radius (TAR) syndrome is a rare genetic disorder.
• It is characterized by radial bone absence and low platelet counts.
• The 1q21.1 region deletion and RBM8A gene variants are implicated.

Purpose of the Study:

• To investigate the role of non-coding RBM8A variants in TAR syndrome.
• To explore the association of a specific 3' UTR variant (c.*6C>T) in RBM8A with TAR syndrome.
• To analyze the impact of this variant on RBM8A transcript stability.

Main Methods:

• Investigated three individuals from two Indian families with TAR syndrome.
• Analyzed the non-coding 3' UTR variant c.*6C>T in the RBM8A gene.
• Utilized an mRNA stability assay to detect RNA degradation.

Main Results:

• The RBM8A c.*6C>T variant was associated with TAR syndrome in the studied families.
• This variant leads to decreased RBM8A transcript stability.
• It acts as a hypomorphic allele when combined with a null allele (1q21.1 deletion).

Conclusions:

• The non-coding RBM8A variant c.*6C>T contributes to TAR syndrome pathogenesis.
• This study is the first to use an mRNA stability assay for non-coding RBM8A variants in TAR syndrome.
• Findings highlight the importance of non-coding regulatory regions in genetic disorders.