A novel mutation in CNNM4 (G492C) associated with Jalili Syndrome

Autor: Christophe Valmaggia, Daniel F. Schorderet, L.T. Lopez Torres, M. G. Todorova
Rok vydání: 2015
Předmět:
Zdroj: Acta Ophthalmologica. 93
ISSN: 1755-375X
Popis: Purpose To describe a new G492C homozygous mutation in a consanguineous family from Saudi Arabia with autosomal recessive cone-rod dystrophy (arCRD) associated with amelogenesis imperfecta and mental deficiency (Jalili syndrome). Methods Both parents and their five children were included in the study. They underwent a complete ophthalmic examination including fundus imaging and optical coherence tomography. Both affected children underwent electrophysiological evaluation including full-field ERG and EOG (ISCEV standard). Direct Sanger sequencing of all exons and intron-exon junctions of CNNM4 was conducted. Results ArCRD was diagnosed in two children with childhood-onset visual impairment and nystagmus. Ophthalmoscopy showed macular atrophy with pigment mottling, attenuated retinal vasculatur and optic disc pallor. Electrophysiology revealed non-recordable scotopic and photopic ERGs, completely attenuated off-response of the on-off ERG and reduced Arden-ratio of the EOG. Both affected children showed mental deficiency and had clinical signs of amelogenesis imperfecta presenting with dysplastic, hypomineralized teeth.Sanger sequencing identified a new c.[1474G>T] mutation in CNNM4, located in exon 2 leading to a substitution of the glycine amino acid to cystein at cDNA position 492. This mutation was homozygous in the two affected children and was heterozygous in the unaffected father, mother and both sisters. One unaffected son was homozygous normal. Conclusions Genetic testing enabled to confirm the diagnosis of Jalili syndrome by identifying a yet unreported G492C mutation in CNNM4.
Databáze: OpenAIRE
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