Our findings indicate that loss of KBP function leads to defects in neuronal migration, morphogenesis, maturation, and survival, which may be responsible for brain phenotypes observed in GOSHS.
We hypothesize that an axonal sensory motor neuropathy may be part of the phenotypical spectrum of KIAA1279-related GOSHS, probably reflecting the effects of reduced KBP protein expression on peripheral neuronal function.
Goldberg-Shprintzen syndrome and the Say-Barber-Biesecker-Young-Simpson type of Ohdo syndrome were suspected but direct sequencing of KBP and KAT6B failed to identify a mutation.
KBP expression directly affected neurite growth in a neuron-like cell line (human neuroblastoma SH-SY5Y), in keeping with the central (polymicrogyria) and enteric (HSCR) neuronal developmental defects seen in GOSHS patients.
KBP expression directly affected neurite growth in a neuron-like cell line (human neuroblastoma SH-SY5Y), in keeping with the central (polymicrogyria) and enteric (HSCR) neuronal developmental defects seen in GOSHS patients.
Recently, we found that KBP, encoded by the gene involved in a HSCR- associated syndrome called Goldberg-Shprintzen syndrome, interacts with SCG10, a stathmin-like protein.
Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.