Genetic teasers 2

An 11 months old boy with infantile spams

He was found to have a likely pathogenic variant, c.251G>A in the SPATA5 gene. This gene is associated with autosomal recessive epilepsy, hearing loss, and intellectual disability. Typically, affected individuals have two pathogenic genetic changes/variants in this gene (one inherited from each parent). Given that only one variant was identified in him, this finding is likely not related to his diagnosis of epilepsy (testing included sequencing and deletion/duplication analysis). However, this result indicates that he is a carrier of SPATA-related epilepsy, hearing loss, and intellectual disability.

He was also found to have a variant of unclear significance, c.225C>G, in the KCNQ3 gene, which is associated with autosomal dominant familial neonatal seizures. This variant has not been previously reported in any affected individuals, but is present in population databases. According to the report, it has a higher allele count than what is expected for a pathogenic variant. At this time the significance of this finding in him is unknown. Another variant of unclear significance, c.815C>T, was identified in the NEDD4L gene, which is associated with autosomal dominant periventricular heterotopia. There is preliminary evidence that suggests that it may also be associated with autosomal dominant early infantile epileptic encephalopathy. This variant has not been reported in affected individuals and is not present in population databases.

See:  http://childnervoussystem.blogspot.com/2016/08/genetic-teasers.html

http://childnervoussystem.blogspot.com/2018/05/i-had-whole-exome-sequencing-performed.html