Molecular and phenotypical features of the Jalili syndrome: A systematic review

Molecular and phenotypical features of the Jalili syndrome: A systematic review
Yousef Daneshmandpour ,¹ Parisa Moeinian ,² Zahra Bahmanpour ,³ Sedigheh Sadat Mortazavi ,⁴ Somayeh Kazeminasab,⁵ Babak Emamalizadeh,^6,*
1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2. Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
3. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4. Division of Genetics, Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
5. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
6. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Introduction: Jalili syndrome (JS) is a rare recessive syndrome that has been reported in all five continents. The first and the Most reported cases of this syndrome are in the Middle East. Patients with JS suffer from two main symptoms, amelogenesis imperfecta (AI) and cone-rod dystrophy (CRD). Nystagmus, photophobia, loss of vision, and tooth decay are the main reported complications in these patients. It has been reported JS patients have mutations in the CNNM4 gene, an mg2+ transporter in the cell. In the current systematic review, previous cases of Jalili syndrome and identified mutations in the CNNM4 gene have been discussed to get to a better understanding of the disease and possible Genotype-phenotype correlations.
Methods: The current systematic review was performed according to the PRISMA statement. Public medical databases including PubMed, Embase, ProQuest, and Cochrane were searched to find published articles. Studies that discussed cases of Jalili syndrome and/or reported its mutations were included in the study.
Results: A total of 3473 studies were identified in search of databases. Title and abstract of studies were evaluated and 2468 studies were excluded and 25 studies remained. The full text of remaining studies was evaluated and none were removed. To date, a total of 134 patients with Jalili syndrome have been identified. CRD and AI were both simultaneously reported in Jalili syndrome patients. Three other studies have discovered additional symptoms including mental retardation, situs inversus, keratoconus, and muscular overgrowth. There are three reported cases of this syndrome in Pakistan, India, and Gaza which lack molecular evaluation. All cases had mutations in the CNNM4 gene. The protein-protein network of the CNNM4 gene was also evaluated.
Conclusion: The previous cases of the JS were discussed in this article. Due to the limited number of studies, no phenotype-genotype correlation could be concluded. The proteins that are in functional correlation with CNNM4 are also reported in patients with ocular disorders. So, further study on the protein network of the CNNM4 may give a better understanding of the molecular etiology of JS. The JS cases are mostly identified in the countries with higher fluoride concentration in their groundwater. The higher ground fluoride concentration may result in increased mutation level in individuals. Further studies are required to confirm this hypothesis.
Keywords: Jalili syndrome; CNNM4; Cone-rod dystrophy ; Amelogenesis imperfecta