Ankyloblepharon-ectodermal Defects-cleft Lip-palate Syndrome Due to a Novel Missense Mutation in the SAM Domain of the TP63 Gene.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare genetic disease with an autosomal dominant transmission, characterized by several congenital anomalies. Clinical features include ectodermal defects affecting the skin, hair, teeth, nails and sweat glands, associated with typical eyelid fusion in addition to a cleft lip and/or palate. The diagnosis is based on clinical criteria and molecular genetic testing of TP63 gene, the gene related to AEC syndrome. In this context, most reported mutations induce an amino acid change in the sterile alpha motif (SAM) domain, and are predicted to disrupt protein-protein interactions. We here describe the case of a 2-year-old Moroccan girl diagnosed with AEC syndrome on the basis of clinical features. The molecular studies and bioinformatics tools revealed a novel heterozygous missense mutation c.1798G>C (p.Gly600Arg) in exon 14 of the TP63 gene, that was not found in her parents. The molecular analysis and the early diagnosis of this syndrome are important to offer appropriate genetic counseling and management to patients and their families.

Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.

Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis.

Inhabitual autosomal recessive form of dentin dysplasia type I in a large consanguineous Moroccan family.

Dentin dysplasia is a rare autosomal dominant genetic disease characterized by defect of dentin development and the causal gene is DSPP (Dentin Sialophosphoprotein gene). We report in the present study a large Moroccan family in which dentin dysplasia is clearly transmitted as an autosomal recessive trait. Four males and females family members born from healthy consanguineous parents are carriers of the typical features of the dentin dysplasia type I. Polymorphic markers that span the DSPP gene, allowed us to show that this locus is not linked to dentin dysplasia in our family. We also excluded in our family the SMOC2 gene (Sparc Related Modular Calcium Binding Protein 2) which was recently identified as a causal gene in dentin dysplasia type I with microdontia and misshapen teeth. This family represents, a new description of autosomal recessive pattern of inheritance of dentin dysplasia type I. Moreover, this form of dentin dysplasia is not allelic to the autosomal dominant dentin dysplasia and the genetic cause is to be discovered.