Comparison of variants with available databases
In the STU-66 family, only one missense variant in COL4A2 gene (c.461G>A; p.Gly154Glu) previously reported in a disorder related to fluency of language11 was observed in our study. COL4A2 encodes type IV collagen that forms a major structural component of basement membrane and are involved in cerebro-vascular disease that include porencephaly and white matter lesions12,13.
Since the STU-65 family had consanguinity for three generations, we scrutinized homozygous variants first. Only one NLRP11 variant (c.1052G>A; p.Arg351Gln) was present in homozygous condition in both the sibs. NLRP11 is a member of NOD like receptor protein with pyrin domain responsible for formation of inflammasome but it is said to represses NF-κB and type I interferon responses, involved in inflammation pathways14\sout. Neuro-immune and neuro-inflammation has been established as key factors in the development of Autism, where speech is also affected15. NLRP11 could be a possible candidate gene in this family. In addition a recently reported heterozygous variant in NAGPA gene (c.322G>A; p.Glu108Lys; gnomAD database) implicated in stuttering was also observed in sibs.