title: Novel DDR2 mutation identified by whole exome sequencing in a Moroccan patient with spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type.
abstract: Spondylo-meta-epiphyseal dysplasia (SMED), short limb-abnormal calcification type (SMED, SL-AC), is a very rare autosomal recessive disorder with various skeletal changes characterized by premature calcification leading to severe disproportionate short stature. Twenty-two patients have been reported until now, but only five mutations (four missense and one splice-site) in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene has been identified. We report here a novel DDR2 missense mutation, c.370C > T (p.Arg124Trp) in a Moroccan girl with SMED, SL-AC, identified by whole exome sequencing. Our study has expanded the mutational spectrum of this rare disease and it has shown that exome sequencing is a powerful and cost-effective tool for the diagnosis of clinically heterogeneous disorders such as SMED.
authors.affiliation: Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco.|Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Rabat, Morocco.
authors.forename: Maria
authors.initials: M
authors.lastname: Mansouri
authors.affiliation: Medical Genetics Department, İstanbul Medical Faculty, İstanbul University, İstanbul, Turkey.
authors.forename: Hülya
authors.initials: H
authors.lastname: Kayserili
authors.affiliation: Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco.|Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Rabat, Morocco.
authors.forename: Siham Chafai
authors.initials: SC
authors.lastname: Elalaoui
authors.affiliation: Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.affiliation: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Rabat, Morocco.
authors.forename: Jaber
authors.initials: J
authors.lastname: Lyahyai
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco.|Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Rabat, Morocco.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Sefiani
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D002114:Calcinosis / Q000235:genetics* / Q000473:pathology*; D002675:Child, Preschool; D000070818:Discoidin Domain Receptors; D004392:Dwarfism / Q000235:genetics* / Q000473:pathology*; D059472:Exome / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D009018:Morocco; D020125:Mutation, Missense / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D011975:Receptors, Mitogen / Q000235:genetics*
chemical_list: D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: DDR2; exome sequencing; novel mutation; short limb-abnormal calcification type; spondylo-meta-epiphyseal dysplasia