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.