Report of two unrelated families with Jalili syndrome and a novel nonsense heterozygous mutation in CNNM4 gene.

Eur J Med Genet. 2018 Jul;61(7):384-387. Epub 2018 Feb 05

Célia Márcia Fernandes Maia ¹ , Renato Assis Machado ² , Vera Lúcia Gil-da-Silva-Lopes ³ , Elaine Lustosa-Mendes ³ , Priscila Hae Hyun Rim ³ ,

Célia Márcia Fernandes Maia ¹ , Renato Assis Machado ² , Vera Lúcia Gil-da-Silva-Lopes ³ , Elaine Lustosa-Mendes ³ , Priscila Hae Hyun Rim ³ , Verônica Oliveira Dias ¹ , Daniella Reis Barbosa Martelli ¹ , Luciano Sólia Nasser ¹ , Ricardo D Coletta ⁴ , Hercílio Martelli-Júnior ⁵

+ et al

Author information

¹ Health Science Program, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil.
² Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil. Electronic address: renatoassismachado@gmail.com.
³ Department of Medical Genetics, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
⁴ Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.
⁵ Health Science Program, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil; Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.

摘要

Jalili syndrome (JS) is an autosomal recessive disease characterized by a combination of cone-rode retinal dytrophy (CRD) and amelogenesis imperfect (AI). Mutations in cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) gene cause JS. Here we described 2 families (3 members) affected by JS. In the first family, JS was caused by the homozygous p.Leu324Pro (c.971TÂ >Â C) missense mutation and the affected patient developed both CRD and AI. In the second family, a specific combination of a compound heterozygous mutation was found - the p.Leu324Pro (c.971TÂ >Â C) missense transition and the novel p.Tyr581* (c.1743CÂ >Â G) nonsense mutation. The proband showed CRD and AI, but her father just developed eye alterations. Together, these findings suggest that the p.Leu324Pro mutation in homozygosis induces a complete phenotype with both CRD and AI, but in heterozygosis and in composition with the novel p.Tyr581* nonsense mutation in CNNM4 promotes variable clinical expressivity, particularly with lack of dental phenotypes. These different phenotypes could be explained by deletions affecting the proband's homologous allele, epistasia or interactions with environmental factors leading to residual activity of protein.

KEYWORDS: Amelogenesis imperfecta, CNNM4, Cone-rod dystrophy, Jalili syndrome, Mutation

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