title: Osteosclerotic bone dysplasia in siblings with a Fam20C mutation.
abstract: Raine syndrome is an autosomal recessive disorder caused by mutations in the FAM20C gene. FAM20C codes for the human homolog of DMP4, a dentin matrix protein highly expressed in odontoblasts and moderately in bone. DMP4 is probably playing a role in the mineralization process. Since the first case reported in 1989 by Raine et al. 21 cases have been published delineating a phenotype which associates dysmorphic features, cerebral calcifications, choanal atresia or stenosis and thoracic/pulmonary hypoplasia. Kan and Kozlowski suggested the name of Raine syndrome to describe this new lethal osteosclerotic bone dysplasia. All the cases described were lethal during the neonatal period except for the last two reported patients aged 8 and 11 years who presented severe mental retardation. Here we describe two sisters, with an attenuated phenotype of Raine syndrome, who present an unexpectedly normal psychomotor development at ages 4 and 1, respectively. Identification of a homozygous mutation in the FAM20C gene confirmed the Raine syndrome diagnosis, thus contributing to the expansion of the Raine syndrome phenotype. This case report also prompted us to revisit the FAM20 gene classification and allowed us to highlight the ancestral status of Fam20C.
authors.affiliation: Service de Génétique Médicale, CHU Strasbourg, Hôpital de Hautepierre, Avenue Molière, Strasbourg, France. melanie.fradin@chru-strasbourg.fr
authors.forename: Melanie
authors.initials: M
authors.lastname: Fradin
authors.forename: C
authors.initials: C
authors.lastname: Stoetzel
authors.forename: J
authors.initials: J
authors.lastname: Muller
authors.forename: M
authors.initials: M
authors.lastname: Koob
authors.forename: D
authors.initials: D
authors.lastname: Christmann
authors.forename: C
authors.initials: C
authors.lastname: Debry
authors.forename: M
authors.initials: M
authors.lastname: Kohler
authors.forename: M
authors.initials: M
authors.lastname: Isnard
authors.forename: D
authors.initials: D
authors.lastname: Astruc
authors.forename: P
authors.initials: P
authors.lastname: Desprez
authors.forename: C
authors.initials: C
authors.lastname: Zorres
authors.forename: E
authors.initials: E
authors.lastname: Flori
authors.forename: H
authors.initials: H
authors.lastname: Dollfus
authors.forename: B
authors.initials: B
authors.lastname: Doray
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001842:Bone and Bones / Q000473:pathology; D047389:Casein Kinase I; D002648:Child; D002675:Child, Preschool; D002754:Choanal Atresia / Q000235:genetics / Q000378:metabolism; D002972:Cleft Palate / Q000175:diagnosis / Q000235:genetics*; D005094:Exophthalmos / Q000175:diagnosis / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010026:Osteosclerosis / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype
chemical_list: D016326:Extracellular Matrix Proteins; D047389:Casein Kinase I; C524449:FAM20C protein, human