title: Exclusion of the dymeclin and PAPSS2 genes in a novel form of spondyloepimetaphyseal dysplasia and mental retardation.
abstract: Spondyloepimetaphyseal dysplasias (SEMD) represent a heterogeneous group of conditions composed of at least 15 well-defined entities. The classification is based on clinical, radiological and molecular findings. Among them, several conditions also include a mental retardation (MR) syndrome, namely Wolcott-Rallison syndrome, Dyggve-Melchior-Clausen syndrome (DMC) and lysosomal storage disorders. Here, we report on a novel form of SEMD with MR in two Pakistani sisters born to first-cousin parents. SEMD, MR, microcephaly, ataxia, facial dysmorphism and hirsutism of back and legs were noted in the two children. Skeletal findings included flat vertebral bodies with irregular vertebral plates, irregular and flared metaphyses with vertical striations, small and irregular epiphyses, small carpal bones and narrow iliac wings without lacy pelvis iliac crest. Similarities with DMC prompted us to test and eventually exclude the DMC gene, dymeclin, by direct sequencing. Similarly, we excluded the PAPSS2 gene (3'-alpha phosphoadenosine 5'-phosphosulphate synthase 2) responsible for SEMD Pakistani type. The combination of features observed in the two sisters does not fit with any previously reported SEMD and represents therefore a novel form of autosomal recessive SEMD with MR.
authors.affiliation: Département de Génétique et Unité INSERM U393, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.forename: Delphine
authors.initials: D
authors.lastname: Héron
authors.forename: Vincent
authors.initials: V
authors.lastname: El Ghouzzi
authors.forename: Catherine
authors.initials: C
authors.lastname: Prost-Squarcioni
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Aurélia
authors.initials: A
authors.lastname: Jacquette
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.forename: Florence
authors.initials: F
authors.lastname: Pinton
authors.forename: Nathalie
authors.initials: N
authors.lastname: Villeneuve
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kalifa
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D001848:Bone Diseases, Developmental / Q000000981:diagnostic imaging / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007178:Inbreeding; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008831:Microcephaly / Q000000981:diagnostic imaging / Q000235:genetics; D008854:Microscopy, Electron; D009097:Multienzyme Complexes / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D012867:Skin / Q000648:ultrastructure; D013430:Sulfate Adenylyltransferase / Q000235:genetics*; D013577:Syndrome
chemical_list: C477370:DYM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D011506:Proteins; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase