Nablus syndrome: Easy to diagnose yet difficult to solve

Area of Science:

• Genetics
• Human Diseases
• Molecular Biology

Background:

• Nablus syndrome is a rare disorder first described in 2000, characterized by distinct facial features.
• The genetic cause of Nablus syndrome has remained unknown despite previous reports.

Purpose of the Study:

• To investigate the genetic etiology of Nablus syndrome.
• To identify the critical genetic region associated with Nablus syndrome.

Main Methods:

• Comparative microarray analyses were performed on individuals with Nablus syndrome.
• Exome sequencing was conducted on five affected individuals.

Main Results:

• An overlapping 8q22.1 microdeletion was identified in individuals with Nablus syndrome, with a minimal critical region of 1.84 Mb.
• The 8q22.1 microdeletion was found in unaffected individuals, suggesting it is necessary but not sufficient for Nablus syndrome.
• No shared deleterious rare coding variants were found in the critical region, but a common intronic SNP was identified.

Conclusions:

• The 8q22.1 microdeletion is implicated in Nablus syndrome but does not fully explain its occurrence due to incomplete penetrance and variable expressivity.
• Further research involving larger cohorts and advanced genomic techniques is required to elucidate the complex genetic mechanisms underlying Nablus syndrome.