BPTF gene mutation 17q24.2 deletion – microcephaly, developmental and speech delay

Chromatin remodeling is essential for DNA accessibility and gene regulation, and its disruption leads to a variety of disorders. The protein complex NURF (nucleosome remodeling factor) involved in chromatin remodeling is important in regulating fetal development. NURF contains the proteins SNF2L, pRBAP46/48, and BPTF. BPTF, in particular, is expressed throughout the body. The BPTF gene is found on chromosome 17, and mutations of this gene or microdeletions within the 17q24.2 region can result in loss of BPTF. This article describes the symptoms of eight individuals with loss-of-function mutations in the BPTF gene and two with microdeletions, involving 17q24.2, and shows how this gene may be related to brain development.

For all ten patients the loss-of-function mutations or deletions were not inherited from family members, but occurred spontaneously. Symptoms shared by all patients include developmental delay, intellectual disability, speech delay, and postnatal microcephaly (children with an average head size at birth, but reduced head growth as they age). Epilepsy was not observed. These results agree with the assumption that BPTF is important in the development of the brain.

In patients with the 17q24.2 microdeletions the gene PSMD12 may be also deleted. Loss of PSMD12 causes similar symptoms as BPTF, including developmental delay and intellectual disability. PSMD12 loss also causes seizures, as well as cardiac, renal, and genital defects.

The article suggests that the loss of BPTF may cause neurological issues. Loss of BPTF disrupts the functionality of the NURF complex, which affects chromatin remodeling. Proper brain development is tightly regulated by gene expression and chromatin remodeling, so loss of BPTF (a key component in this regulatory process) severely hinders this process. However, more evidence from additional studies is needed to confirm this assumption.

Stankiewicz, et al. “Haploinsufficiency of the Chromatin Remodeler BPTF Causes Syndromic Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features”. The American Journal of Human Genetics. 2017, v. 101, 503-515.