1. A New SLC10A7 Homozygous Missense Mutation Responsible for a Milder Phenotype of Skeletal Dysplasia With Amelogenesis Imperfecta
- Author
-
Laugel-Haushalter, Virginie, Bär, Séverine, Schaefer, Elise, Stoetzel, Corinne, Geoffroy, Véronique, Alembik, Yves, Kharouf, Naji, Huckert, Mathilde, Hamm, Pauline, Hemmerlé, Joseph, Maniere, Marie-Cécile, Friant, Sylvie, Dollfus, Hélène, Bloch-Zupan, Agnès, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire, génomique, microbiologie (GMGM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Clinique [Hautepierre Strasbourg], Hôpital de Hautepierre [Strasbourg], Faculté de chirurgie dentaire - Strasbourg, Université de Strasbourg (UNISTRA), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nanomédecine Régénérative (NanoRegMed), and Les Hôpitaux Universitaires de Strasbourg (HUS)
- Subjects
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,NGS (next generation sequencing) ,Genetics ,rare diseases ,Sciences du Vivant [q-bio]/Biotechnologies ,Case Report ,amelogenesis imperfecta ,human ,skeletal dysplasia ,Sciences du Vivant [q-bio]/Génétique - Abstract
International audience; Amelogenesis imperfecta (AI) is a heterogeneous group of rare inherited diseases presenting with enamel defects. More than 30 genes have been reported to be involved in syndromic or non-syndromic AI and new genes are continuously discovered (Smith et al., 2017). Whole-exome sequencing was performed in a consanguineous family. The affected daughter presented with intra-uterine and postnatal growth retardation, skeletal dysplasia, macrocephaly, blue sclerae, and hypoplastic AI. We identified a homozygous missense mutation in exon 11 of SLC10A7 (NM_001300842.2: c.908C>T; p.Pro303Leu) segregating with the disease phenotype. We found that Slc10a7 transcripts were expressed in the epithelium of the developing mouse tooth, bones undergoing ossification, and in vertebrae. Our results revealed that SLC10A7 is overexpressed in patient fibroblasts. Patient cells display altered intracellular calcium localization suggesting that SLC10A7 regulates calcium trafficking. Mutations in this gene were previously reported to cause a similar syndromic phenotype, but with more severe skeletal defects (Ashikov et al., 2018;Dubail et al., 2018). Therefore, phenotypes resulting from a mutation in SLC10A7 can vary in severity. However, AI is the key feature indicative of SLC10A7 mutations in patients with skeletal dysplasia. Identifying this important phenotype will improve clinical diagnosis and patient management.
- Published
- 2019
- Full Text
- View/download PDF