New Insights Into TRMT10A Syndrome: Case Report and Literature Review

Area of Science:

• Genetics and Molecular Biology
• Neuroscience
• Metabolic Disorders

Background:

• TRMT10A gene mutations are linked to a syndrome featuring early-onset diabetes, microcephaly, epilepsy, and intellectual disability.
• The TRMT10A gene encodes a methyltransferase crucial for methylation and S-adenosylmethionine metabolism, impacting mitochondrial and glucose functions.

Purpose of the Study:

• To report a novel case expanding the clinical and genetic spectrum of TRMT10A-related syndrome.
• To investigate the association between TRMT10A variants and neurological phenotypes, particularly brain malformations.

Main Methods:

• Clinical case report detailing patient's neurological presentation.
• Genetic analysis to identify causative mutations in the TRMT10A gene.
• Functional analysis of the identified mutation's impact on the TRMT10A protein domain.

Main Results:

• A homozygous c.421-1G>A variant in TRMT10A, affecting a splicing site, was identified as causative.
• The mutation disrupts the SAM-dependent methyltransferase TRM10-type domain, impacting methylation processes.
• The patient presented with spastic-ataxic paraparesis and Dandy-Walker variant, highlighting significant neurological involvement.

Conclusions:

• This case expands the known clinical spectrum of TRMT10A syndrome to include spastic-ataxic paraparesis and cerebellar malformations.
• TRMT10A plays a critical role in brain development, and its variants may be associated with dominant neurological phenotypes.
• Further research is needed to understand the pathogenic mechanisms and explore therapeutic strategies for TRMT10A-related disorders.