Identification of two aberrant transcripts by RNA sequencing for a novel variant c.3354 + 5 G > A of MED12 in a Chinese girl with non-syndromic intellectual disability

•The variant spectrum of MED12 is expanded.•Two aberrant transcripts were identified by RNA sequencing.•The milder clinical feature may be caused by multiple different transcripts.•RNA sequencing is essential for splice variants to detect the effect on transcriptome. Missense variants in MED12 are associated with MED12-related disorders. We aimed to clarify the molecular level changes and underlying pathogenic mechanism of a female patient in our study. We reported a Chinese girl with clinical characteristics similar to MED12-related disorders. Trio whole exome sequencing (WES) was performed to identify related pathogenic variant(s) and RNA sequencing (RNA-seq) was subsequently applied to evaluate the effect of identified variant(s) on mRNA splicing. Moreover, X-chromosome inactivation (XCI) assay based on AR and RP2 was performed to reveal the XCI pattern of the female patient. The proband manifested mainly as mental retardation and language impairment. Trio WES revealed a novel heterozygous variant c.3354 + 5 G > A in intron 23 of MED12. RNA-seq identified two aberrant transcripts. XCI assay on AR revealed a homozygous result, while XCI based on RP2 showed random pattern in peripheral blood. In conclusion, we identified a novel variant c.3354 + 5 G > A by WES combined with RNA-seq, which extends the spectrum of MED12 variants and provide a basis for further genetic counseling. According to the result of two aberrant transcripts by RNA-seq, we speculate that our patient’s milder clinical feature may be the consequence of multiple different transcripts.