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

Abstract Background Genetic variants involving the MED13L gene can lead to an autosomal dominant syndrome characterised by intellectual disability/developmental delay and facial dysmorphism. Methods We investigated two cases (one familial and one isolated) of intellectual disability with speech delay and dysmorphic facial features by whole‐exome sequencing analyses. Further, we performed a literature review about clinical and molecular aspects of MED13L gene and syndrome. Results Two MED13L variants have been identified [ MED13L (NM_015335.5):c.4417C>T and MED13L (NM_015335.5):c.2318delC] and were classified as pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines. One of the variants was present in sibs. Conclusions The two pathogenic variants identified have not been previously reported. Importantly, this is the first report of a familial case of MED13L nonsense mutation. Although the parents of the affected children were no longer available for analysis, their apparently normal phenotypes were surmised from familial verbal descriptions corresponding to normal mental behaviour and phenotype. In this situation, the familial component of mutation transmission might be caused by gonadal mosaicism of a MED13L mutation in a gonad from either the father or the mother. The case reports and the literature review presented in this manuscript can be useful for genetic counselling.