RECURRENT RAB3GAP1 MUTATIONS IN THE TURKISH POPULATION

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Ophthalmology

Background:

• Warburg Micro Syndrome (WARBM) is a rare, severe autosomal recessive neurodevelopmental disorder.
• It is characterized by microcephaly, microphthalmia, microcornea, congenital cataract, cortical dysplasia, corpus callosum hypoplasia, intellectual disability, hypotonia, and hypogonadism.
• Mutations in RAB3GAP1 and RAB3GAP2 genes, encoding RAB3GTPase-activating protein, are implicated in WARBM, affecting brain, eye, and genitalia development.

Observation:

• This study investigated recurrent RAB3GAP1 mutations and clinical features in Turkish patients with WARBM.
• Two brothers from a non-consanguineous Turkish family presented with clinical features consistent with WARBM.
• The c.748+1G>A splice-site mutation in RAB3GAP1 intron 8 was identified and found to be common in this family.

Findings:

• The c.748+1G>A splice-site mutation in RAB3GAP1 is recurrent and appears to be prevalent in Turkish patients with WARBM.
• This mutation has so far only been detected in patients of Turkish ethnic origin.
• No specific phenotypic findings were uniquely associated with this mutation, despite minor variations like an extra finger crease or nephrolithiasis in one patient.

Implications:

• The findings highlight the importance of genetic analysis in diagnosing WARBM, particularly in populations with recurrent mutations.
• Understanding the prevalence of specific mutations like c.748+1G>A in certain ethnic groups can aid in genetic counseling and diagnosis.
• Further research may elucidate genotype-phenotype correlations for RAB3GAP1 mutations in WARBM.