Three Japanese patients with 3p13 microdeletions involving FOXP1

Area of Science:

• Genetics and Developmental Biology
• Human Molecular Genetics

Background:

• The Forkhead box P1 (FOXP1) gene is crucial for neurodevelopment, with loss-of-function mutations linked to intellectual disability and language impairment.
• Clinical manifestations associated with FOXP1 dysfunction include feeding difficulties, hypotonia, and distinct facial features.
• The 3p13 microdeletion syndrome frequently involves the FOXP1 gene, leading to overlapping phenotypes and the proposed designation of "FOXP1-related intellectual disability syndrome".

Purpose of the Study:

• To report the first cases of 3p13 microdeletions involving FOXP1 in Japanese patients.
• To characterize the clinical phenotype associated with 3p13 microdeletions in this cohort.
• To evaluate the clinical recognizability of "FOXP1-related intellectual disability syndrome".

Main Methods:

• Chromosomal microarray analysis was performed on patients with unexplained etiologies after obtaining informed consent.
• Genetic testing identified three Japanese patients with 3p13 microdeletions encompassing the FOXP1 gene.

Main Results:

• Three Japanese patients with 3p13 microdeletions involving FOXP1 were identified.
• All patients exhibited growth delay, moderate to severe developmental delay, hearing loss, and characteristic facial features (prominent forehead, mid-facial hypoplasia).
• A 'square-shaped face' was a commonly observed feature across all three patients, potentially representing a novel characteristic finding.

Conclusions:

• This study presents the initial report of 3p13 microdeletions involving FOXP1 in Japan.
• The consistent clinical features, including developmental delay and distinctive facial morphology, support the recognition of "FOXP1-related intellectual disability syndrome" as a clinically identifiable condition.
• The identification of a 'square-shaped face' may aid in the clinical diagnosis of this syndrome.