Phenotype Heterogeneity in 3q29 Microduplication Syndrome.

Area of Science:

• Genetics
• Neuroscience
• Immunology

Background:

• 3q29 microduplication syndrome typically presents with variable, often mild, clinical features.
• Commonly observed features include developmental delay, intellectual disability, and congenital abnormalities, but a distinct pattern is elusive.

Purpose of the Study:

• To report a unique case of 3q29 microduplication syndrome with late onset.
• To investigate the genetic underpinnings of the observed clinical manifestations.

Main Methods:

• Array comparative genomic hybridization (aCGH) was used to identify a 1.65Mb duplication at 3q29.
• Clinical data from a 34-year-old female patient was analyzed.

Main Results:

• A 1.65Mb duplication at 3q29 was identified in a 34-year-old woman with mild intellectual disability, progressive cortical atrophy, and recurrent mucosal candidiasis.
• The duplicated region contains 29 genes, including PAK2, DLG1, BDH1, FBXO45, and TFRC, implicated in neuronal development and synaptic function.
• The gene RNF168 is a potential candidate for the observed immunodeficiency.

Conclusions:

• This case expands the phenotypic spectrum of 3q29 microduplication syndrome, particularly regarding late onset and immunodeficiency.
• Further research is necessary to elucidate the complex pathophysiological mechanisms underlying this rare genetic disorder.