SETBP1 related developmental delay is caused by haploinsufficiency of SETBP1 which may be caused by either a loss of function mutation or an 18q12.3 deletion. The latter may comprise (a part of) SETBP1 only or consist of a larger contiguous gene deletion including SETBP1 and one or more other genes. The SETBP1 gene provides instructions for a protein called SET binding protein 1. This protein binds the SET nuclear oncogene, involved in DNA replication. The gene is shown to be expressed in numerous tissues including the brain and multiple transcript variants encoding different isoforms have been found. The function of this protein is still largely unknown. This 18q12.3 microdeletion causes SETBP1 haploinsufficiency.
Based on information about a limited amount of individuals, it seems disruptive mutations in SETBP1 are highly penetrant for completely absent or substantially impaired speech and language development.
Diagnostic testing is performed by sequence analysis of the entire coding region of SETBP1 and deletion/duplication analysis of the chromosome 18q12.3 region.
It may be useful to test for SETBP1 microdeletion in patients with developmental delay or learning problems and speech impairment with major motor speech problems.