9p13.2 deletion, the PAX5 gene and the brain

chromosome 9

9p13.2 and the PAX5 gene. Mutation or deletion of this gene causes a novel neurodevelopmental disorder.

The clinical consequences of deletions of the distal part of 9p are well known. At the same time the
significance of interstitial deletions of other areas of 9p are not so clear. The segment 9p13.2
includes the PAX5 gene. It is known that during mouse embryogenesis this gene is expressed in
the mesencephalon (midbrain) and spinal cord. Therefore it may be expected that a malfunction of this
gene may affect the function of the human brain. The authors collected information about 16
individuals with deletions of the 9p13.2 (involving PAX5 and some neighboring genes) and with
point mutations of this gene. The size of deletions varied between 2.5 Mb and 3.7 Mb. Among patients
with deletions there were three brothers from one family who suffered from autism spectrum
disorder (ASD), one unrelated 17-year-old male with seizures, ASD and developmental delay and
one boy with developmental disability, short stature and feeding difficulties. His brain MRI was
normal. Neither of these 5 patients had defects of the visceral organs. Basically the same clinical
spectrum (ASD, seizures, developmental delay) was found in 11 patients with mutations in the
PAX5 gene. The authors conclude that the malfunction of this gene (either due to deletion or due to
mutation) causes a novel neurodevelopmental syndrome (but basically no other anomalies).
The similarity of manifestations in patients with mutations and deletions also affecting several
neighboring genes shows that the absence of neighboring genes does not cause any specific clinical
defects.

Gofin Y. et al. “Delineation of a novel neurodevelopmental syndrome associated with
PAX5 haploinsufficiency”. “Human Mutation” 2022, v. 43, 461-470.