Identification of a Novel Mutation in CNNM4 Gene in an Iranian Family with Jalili Syndrome

Jalili syndrome is a rare autosomal recessive genetic disorder, which so far, only 33 families with this disorder have been reported worldwide. Patients with this disease simultaneously develop cone-rod retinal dystrophy (CRD) and amelogenesis imperfecta (AI). In this study, a mutation causing Jalili syndrome, was investigated in an Iranian family.
 
Case Report: The cases were two brothers with Jalili syndrome in an Iranian family, in whom, the sequence of causative gene (CNNM4), was identified. Their parents were not consanguineous and lived in a small village in East Azerbaijan, northwest of Iran. Both patients had enamel destruction since childhood. Ocular symptoms began in their adolescence and eventually led to photophobia, color blindness, and central vision loss  amelogenesis imperfecta from childhood. Ocular symptoms began in adolescence with photophobia, achromatopsia, and central vision loss, which their vision gradually deteriorated in dim light and at night. Currently, the patients have very limited vision. In electroretinography of the proband, cone-rod degeneration, was diagnosed. A novel variant (c.1220G>T) was found by Sanger sequencing of CNNM4 in proband, which is segregated in the pedigree. This change may be due to replacement of arginine 407 with leucine (Arg407Leu). Analysis by pathogenesis predictive softwares, confirmed the involvement of this change in the development of Jalili syndrome in this family (this variation was not reported in the Exome Aggregation Consortium (ExAC) and 1000 genome databases. Arginine 407 has been conserved in several species.