A novel exon 17 deletion mutation of RPGRIP1 gene in two siblings with Leber congenital amaurosis.

Purpose: To investigate mutations of causal genes in two affected male siblings of a Japanese family with suspected Leber congenital amaurosis (LCA) and to characterize the related clinical features.

Methods: After obtaining informed consent, genomic DNA was extracted from peripheral blood of the proband and his family members. Mutation screening was initially performed with microarrays. The PCR and direct sequencing were successively done for confirmation of mutation detected by microarray, and the two patients who are the subjects of this study were also clinically examined.

Results: Results of the microarray suggested deletion of exon 17 of RPGRIP1. Confirmation by PCR and direct sequencing following microarray analysis revealed that both siblings had homozygous deletion of exon 17 of the RPGRIP1 gene, while their unaffected parents were heterozygous carriers. Length of the deletion was 1339 bp including exon 17 at the position of c.2710+372_2895+76del1339. Clinical features of the two siblings showed nystagmus, poor visual acuity, hyperopia, and photophobia since early childhood; but there was no oculo-digital sign, vessel attenuation or RPE mottling from the mid-retina to the periphery. Full-field single flash ERG was recordable but 30 Hz flicker ERG was not detectable.

Conclusions: Although the present patients did not show sufficient clinical findings as LCA, PCR findings and direct sequencing following microarray analysis confirmed that they were LCA. Genetic analyses are helpful for confirmation of clinical diagnosis.