ClinVar

In a boy with Waardenburg syndrome type 2E (611584), Sznajer et al. (2008) identified a heterozygous de novo A-to-C transversion in intron 4 of the SOX10 gene. In addition to sensorineural deafness and vivid blue eyes, he had neurologic abnormalities, including white matter anomalies, mental retardation with autistic-like behavior, hypotonia, and a generalized peripheral neuropathy. Brain imaging showed complete agenesis of the semicircular canals. Hirschsprung disease was absent. Sznajer et al. (2008) hypothesized that the mutation decreased the strength of the acceptor splice site and increased the strength of at least 1 cryptic site 5 nucleotides downstream. Utilization of this cryptic site would cause a frameshift and premature termination 46 residues downstream. The mutation was not present in either parent or in 300 control chromosomes.