Abstract:

Neurodevelopmental disorders (NDDs) have strong clinical heterogeneity and complex genotype-phenotype correlation. To improve clinicians' understanding of the genotype-phenotype correlation of SHANK2, this study reported the patients presenting with different degrees of NDDs and carrying three combinations of SHANK2 variations from the same family. A total of 4 patients in the 2 generations of this family showed mild to severe mental retardation. Genetic testing found SHANK2 gene variations, including monoallelic variation c.2309-2A>C (mother) and monoallelic exon 11-16 deletion (father), and two children (the proband and his second sister) who carried the biallelic variations. The father with the monoallelic deletion variation showed mild intellectual disability, the mother with the monoallelic c.2309-2A>C variation showed moderate intellectual disability, and the two patients with the biallelic variations manifested severe intellectual disability. The severity of SHANK2-related NDDs may be associated with SHANK2 quantity dependence, and this quantity dependence provides help for understanding the genotype-phenotype correlation of SHANK2-related NDDs.

Key words: SHANK2 gene, developmental disorders, quantity dependence