Nonrecurrent 17p duplications in two patients with developmental and neurological abnormalities

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• Variable copy number variations (CNVs) on chromosome 17p are associated with neurodevelopmental disorders like Charcot-Marie-Tooth disease type 1A.
• These CNVs can lead to conditions such as Potocki-Lupski syndrome and Yuan-Harel-Lupski syndrome.

Purpose of the Study:

• To investigate copy number variations (CNVs) in two sporadic cases presenting with developmental abnormalities, brain impairment, and peripheral neuropathy.
• To identify novel genetic alterations on chromosome 17p associated with these complex phenotypes.

Main Methods:

• Analysis of copy number variations (CNVs) in two patients with unexplained developmental and neurological symptoms.
• Characterization of the size and genetic content of identified duplications on chromosome 17p.

Main Results:

• Identification of novel duplications of approximately 14.1 Mb at 17p11.2-p13.1 and 17.6 Mb at 17p11.2-p13.3 in the two patients.
• The identified duplications encompass key genes including PMP22, RAI1, YWHAE, and PAFAH1B.
• Evidence suggests these duplications arose from de novo mutations of paternal origin.

Conclusions:

• Copy number variations (CNVs) on chromosome 17p are implicated in a spectrum of neurodevelopmental and neurological disorders.
• Genetic screening for 17p CNVs is recommended for patients presenting with peripheral neuropathy alongside developmental and brain abnormalities.