PCDHGC4 is the first member of the protein family of clustered protocadherins that has been linked to a congenital human disorder. An international research collaboration led by scientists from Göttingen has identified eight biallelic variants in PCDHGC4 as genetic cause of a novel neurodevelopmental disorder with progressive microcephaly, intellectual disability, developmental delay, joint anomalies and seizures in 19 patients from nine unrelated families.

Protocadherins are calcium-dependent cell adhesion molecules which mediate cell-to-cell contacts. They are predominantly expressed in the central nervous system and involved in many neurodevelopmental processes. Clustered protocadherins are encoded by 53 genes arranged in three clusters in a single genomic region. They endow each neuron with a specific cell identity code that allows the neuron to discriminate self from non-self, an essential prerequisite for the assembly of neuronal circuits.

The results of the study have been published in Genetics in Medicine