A novel mutation and variable phenotypic expression in a large consanguineous pedigree with Jalili syndrome

Abstract

Purpose Jalili syndrome is an autosomal recessive disorder characterized by simultaneous appearance of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI). Mutations in CNNM4 gene have been identified as the underlying cause of the syndrome. In this study, we investigated a large affected family to identify the causative mutation. Patients and Methods A seven-generation family with 24 members affected with Jalili syndrome were enrolled in the study. Comprehensive ophthalmologic and dental examinations were performed on them. The entire coding region of CNNM4 gene was sequenced for detection of potential mutations. Results Ocular examinations showed nystagmus and photophobia along with early onset visual impairment. Fundoscopic exams revealed a spectrum of macular dystrophies in different family members, from macular coloboma and advanced form of beaten bronze macular dystrophy (bull's eye) to milder form of macular thinning along with a range of pigmentary changes and vascular attenuation in the posterior pole and periphery. Scotopic and photopic electroretinographic responses (ERGs) were extinguished or significantly depressed. Mutation analysis revealed a novel mutation (c.1091delG) in homozygous form in the patients and as a heterozygous form in the normal carrier subjects. Conclusion We identified a novel homozygous deleterious mutation in CNNM4 gene which causes Jalili syndrome.

Novel homozygous nonsynonymous variant of CNNM4 gene in a Chinese family with Jalili syndrome

“…Refractive error was unavailable due to the opaque lens of the two patients in this study. In other literatures, mild to moderate hyperopia, and posterior capsular cataracts were common among JS patients (Rahimi-Aliabadi et al, 2016;Wawrocka et al, 2017). In addition, strabismus and keratoconus were reported in a few cases (Maia et al, 2018;Purwar et al, 2015).…”

A novel pathogenic missense variant in CNNM4 underlying Jalili syndrome: Insights from molecular dynamics simulations

“…CNNM4 mutations have revealed clinical consequences which are limited to retinal function in CRD and bio‐mineralization of teeth in AI (Parry et al, ). Twenty‐four CNNM4 mutations, including a single base insertion, base pair duplication, missense changes, large deletions, and termination mutations have been characterized in patients suffering from JS around the world (Abu‐Safieh et al, ; Coppieters et al, ; Doucette et al, ; Huang et al, ; Jaouad et al, ; Kiessling, Mitter, Mitter, Langmann, & Müller, ; Lopez Torres, Schorderet, Schorderet, Valmaggia, & Todorova, ; Luder et al, ; Maia et al, ; Polok et al, ; Prasad et al, ; Rahimi‐Aliabadi et al, ; Topçu et al, ; Wang et al, ; Wawrocka et al, ; Zobor et al, ). These mutations presumably influence the divalent metal transporter function of CNNM4 protein.…”

Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1

“…A total of twenty-four CNNM4 mutations have been documented to cause Jalili syndrome (OMIM # 217080), a rare condition consisting of cone-rod dystrophy and amelogenesis imperfecta (AI) (http://jalili.co/CNNM4/cnnm4_muts&stats.htm; Michaelides et al 2004; Parry et al 2009; Polok et al 2009; Jalili 2010; Zobor et al 2012; Abu-Safieh et al 2013; Doucette et al 2013; Luder et al 2013; Coppieters et al 2014; Gerth-Kahlert et al 2015; Wang et al 2015; Prasad et al 2016; Rahimi-Aliabadi et al 2016; Topcu et al 2016; Cherkaoui Jaouad et al 2017). While our initial evaluation of the present family did not identify the AI, reassessment uncovered the severe dental abnormalities that necessitated extraction of all teeth and the fitting of dentures in affected, but not in unaffected siblings or parents.…”