Two novel pathogenic variants in MED13L: one familial and one isolated case

Area of Science:

• Genetics
• Molecular Biology
• Human Disease

Background:

• Genetic variants in the MED13L gene are associated with autosomal dominant disorders.
• These syndromes are characterized by intellectual disability, developmental delay, and facial dysmorphism.

Observation:

• Whole-exome sequencing identified two novel pathogenic MED13L variants (c.4417C>T and c.2318delC).
• One variant was identified in a familial case, suggesting autosomal dominant inheritance.
• This is the first reported familial case of a MED13L nonsense mutation.

Findings:

• Two previously unreported pathogenic MED13L variants were identified and classified according to ACMG guidelines.
• The familial case involved a MED13L nonsense mutation, with affected siblings.
• Parents were unavailable for analysis, but normal phenotypes suggest potential gonadal mosaicism.

Implications:

• These findings expand the known spectrum of MED13L pathogenic variants.
• The identification of gonadal mosaicism offers insights into inheritance patterns for MED13L disorders.
• This research provides valuable information for genetic counseling regarding MED13L-related conditions.