10p12.1 deletion and the WAC gene

Chromosome 10p12.1 deletion and the affect of the WAC gene

The short arm of chromosome 10 contains the WAC gene, located at 10p12.1. A loss of function of
this gene causes DeSanto-Shinawi syndrome (DESSH) which is characterized by facial dysmorphism,
global developmental delay and behavioral abnormalities. Patients with deletions of this
segment of chromosome 10 involving the WAC gene reveal similar clinical manifestations. The
Spanish authors (Toledo-Gotor et al.) reported a 6-year-old girl with intellectual impairment,
language delay, enuresis, synophrys, preauricular pits and other dysmorphic features. A cytogenetic
examination of this girl showed a 2.49 Mb deletion 10p12.1p11.23, including the WAC gene. The
geneticists from Turkey (Bolat et al.) presented a 9-year-old boy with developmental delay, autism
spectrum disorder, attention deficit disorder, short neck, dysmorphic features, hypertrichosis,
inguinal hernia, cryptorchidism and mild abnormalities of the brain revealed by MRI. Cytogenetic
examination revealed a 2.8 Mb deletion 10p12.1p11.23, also involving the WAC gene. Several
patients with deletions of chromosome 10p affecting the WAC gene are known from literature. Both groups of
authors compare manifestations in patients with deletions and in patients with DESSH caused by
mutations. The frequency of growth and motor delay, intellectual disability, sleep disturbances and
some dysmorphic features are very similar in both groups. There are some differences in the frequency
of features such as prominent forehead, synophrys or preauricular pits but neither of these
differences seems to be significant due to the low number of known patients. Many patients with
deletions have congenital heart disease which is not characteristic for DESSH; most likely heart
defects are caused by deletions of neighboring genes. Additional observations on patients with
deletions of this area of 10p and point mutations of the WAC gene are necessary to resolve the
diagnostic problem.

Toledo-Gotor C. et al. “Phenotypic comparison of patients with DeSanto-Shinawi
syndrome: point mutations in WAC gene versus a 10p12.1 microdeletion including
WAC”. “Mol. Genet. Genomic Med.” 2022, online.
Bolat H. et al. “Phenotypic and brain imaging findings associated with a 10p proximal
deletion including the WAC gene: case report and literature review”. “Cogn. Behav.
Neurol.” 2022, online.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact info@chromodisorder.org