Genes encoding
proteins critical for intracellular vesicular transport are an emerging area of importance for neurologists. In particular,
proteins that create and maintain the correct compartmental pH, such as the endosomal
Na(+)/H(+) exchangers (NHEs), have been implicated in a wide range of human diseases, including cardiovascular, inflammatory bowel, renal, and
neurologic disorders, which demonstrates the critical cellular function of these proteins.(1-3) Two NHEs, NHE6 and NHE9, have been linked to
neurologic disorders in children.(4) Pathologic variants in SLC9A6 encoding NHE6 cause an Angelman-like disorder called
Christianson syndrome. Fewer variants have been described in SLC9A9 encoding NHE9, but individuals carrying these variants have been diagnosed with
neurologic disorders ranging from
autism to
epilepsy to
attention-deficit/hyperactivity disorder. The majority of described variants are missense, resulting in amino acid substitutions, making it difficult to determine their functional consequence.(4).