title: IMPAD1 mutations in two Catel-Manzke like patients.
abstract: Catel-Manzke syndrome is characterized by hyperphalangism with bilateral deviation of the index fingers and micrognathia with or without cleft palate. Some atypical patients present with additional malformations. No molecular basis is yet available. Most patients have an unremarkable family history but autosomal recessive inheritance has been recently suggested in a consanguineous family with recurrence in sibs. Catel-Manzke syndrome has overlapping features with Desbuquois dysplasia type 1 due to CANT1 (calcium-activated nucleotidase 1) mutations and also with "chondrodysplasia with joint dislocations, gPAPP type" due to IMPAD1 (Inositol Monophosphatase Domain containing 1) mutations recently reported in four patients, all characterized by short stature, joint dislocations, brachydactyly and cleft palate. The aim of our study was to screen CANT1 and IMPAD1 in Catel-Manzke patients. Three patients were diagnosed as classical Catel-Manzke syndrome and two as Catel-Manzke like patients, based on the presence of additional features. We identified two homozygous loss-of-function IMPAD1 mutations in the two Catel-Manzke like patients (p.Arg187X and p.Ser108ArgfsX48). The phenotype was characterized by severe growth retardation with short and abnormal extremities, cleft palate with micrognathia and knee hyperlaxity. Radiographs of hands and feet revealed numerous accessory bones with abnormally shaped phalanges and carpal synostosis. Based on this report, we concluded that IMPAD1 should be screened for patients with Catel-Manzke and additional features.
authors.affiliation: Département de génétique, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Nizon
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Alanay
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tuysuz
authors.forename: Pelin Ozlem Simsek
authors.initials: PO
authors.lastname: Kiper
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.forename: David
authors.initials: D
authors.lastname: Sillence
authors.forename: Celine
authors.initials: C
authors.lastname: Huber
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D006228:Hand Deformities, Congenital / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D010855:Pierre Robin Syndrome / Q000201:enzymology / Q000235:genetics*
chemical_list: D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase