title: Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1 mutations.
abstract: Opitz syndrome (OS; MIM 145410 and MIM 300000) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal (LTE) abnormalities, imperforate anus, developmental delay, and cardiac defects. The X-linked form (XLOS) is caused by mutations in the MID1 gene, which encodes a microtubule-associated RBCC protein. In this study, phenotypic manifestations of patients with and without MID1 mutations were compared to determine genotype-phenotype correlations. We detected 10 novel mutations, 5 in familial cases, 2 in sporadic cases, and 3 in families for whom it was not clear if they were familial or sporadic. The genotype and phenotype was compared for these 10 families, clinically diagnosed OS patients found not to have MID1 mutations, and 4 families in whom we have previously reported MID1 mutations. This combined data set includes clinical and mutation data on 70 patients. The XLOS patients with MID1 mutations were less severely affected than patients with MID1 mutations reported in previous studies, particularly in functionally significant neurologic, LTE, anal, and cardiac abnormalities. Minor anomalies were more prevalent in patients with MID1 mutations compared to those without mutations in this study. Female MID1 mutation carriers had milder phenotypes compared to male MID1 mutation carriers, with the most common manifestation being hypertelorism in both sexes. Most of the anomalies found in the patients of the present study do not correlate with the MID1 mutation type, with the possible exception of LTE malformations. This study demonstrates the wide spectrum of severity and manifestations of OS. It also shows that XLOS patients with MID1 mutations may be less severely affected than indicated in prior reports.
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Joyce
authors.initials: J
authors.lastname: So
authors.forename: Vanessa
authors.initials: V
authors.lastname: Suckow
authors.forename: Zofia
authors.initials: Z
authors.lastname: Kijas
authors.forename: Vera
authors.initials: V
authors.lastname: Kalscheuer
authors.forename: Bettina
authors.initials: B
authors.lastname: Moser
authors.forename: Jennifer
authors.initials: J
authors.lastname: Winter
authors.forename: Marieke
authors.initials: M
authors.lastname: Baars
authors.forename: Helen
authors.initials: H
authors.lastname: Firth
authors.forename: Peter
authors.initials: P
authors.lastname: Lunt
authors.forename: Ben
authors.initials: B
authors.lastname: Hamel
authors.forename: Peter
authors.initials: P
authors.lastname: Meinecke
authors.forename: Claude
authors.initials: C
authors.lastname: Moraine
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Albert
authors.initials: A
authors.lastname: Schinzel
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Smagt
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Beate
authors.initials: B
authors.lastname: Albrecht
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Ineke
authors.initials: I
authors.lastname: van der Burgt
authors.forename: Fred
authors.initials: F
authors.lastname: Petrij
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Julie
authors.initials: J
authors.lastname: McGaughran
authors.forename: Fiona
authors.initials: F
authors.lastname: McKenzie
authors.forename: John M
authors.initials: JM
authors.lastname: Opitz
authors.forename: Timothy
authors.initials: T
authors.lastname: Cox
authors.forename: Susann
authors.initials: S
authors.lastname: Schweiger
mesh_terms: D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006801:Humans; D008297:Male; D008868:Microtubule Proteins / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: D008868:Microtubule Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases