Título / Title

REPORT OF TWO UNRELATED FAMILIES WITH JALILI SYNDROME AND A NOVEL NONSENSE HETEROZYGOUS MUTATION IN CNNM4 GENE

Introdução / Purpose

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. Genetic sequencing was performed in the members of both families and the result was compared with the reports in the current medical literature.

Material e Método / Methods

Genetic analysis of CNNM4 gene: Genomic DNA was isolated from the buccal mucosa cells. Direct DNA sequencing of
PCR products was performed. The CNNM4 gene was amplified by polymerase chain reaction (PCR). Electroretinogram, optic coherence tomography and retinography were performed in all affected patients

Resultados / Results

Family A: mutational screening of the affected patient showed a homozygous T to C transition at position 971 (NM_020184.3:
c.971T > C), which lead to the change of a leucine (Leu) for a proline (Pro) in the codon 324 (p.Leu324Pro).
Family B: the affected members of this family (proband and her father) demonstrated a compound mutation in CNNM4: the
p.Leu324Pro mutation in exon 1 and the undescribed mutation represented by a C for G substituition at nucleotide 1743 (NM_020184.3:c.1743C > G).

Discussão e Conclusões / Conclusion

Since the first identification of the CNNM4 mutation in patients with JS (Jaliliand Smith, 1988), 22 different mutations have been reported. The findings of the clinical and genetic evaluations confirmed the presence of mutations in the CNNM4 gene, with phenotype-genotypic variation, suggesting that epistatic events, environmental effects or remaining protein activity may modulate the clinical variations and severity of the syndrome of Jalili. Faced with ocular, dental and genetic confirmations, these two families characterize the first described cases of Jalili's syndrome in Brazil.

Palavras Chave

Jalili syndrome, Cone-rod dystrophy, Amelogenesis imperfecta, CNNM4, Mutation.