title: Screening of CD96 and ASXL1 in 11 patients with Opitz C or Bohring-Opitz syndromes.
abstract: Opitz C trigonocephaly (or Opitz C syndrome, OTCS) and Bohring-Opitz syndrome (BOS or C-like syndrome) are two rare genetic disorders with phenotypic overlap. The genetic causes of these diseases are not understood. However, two genes have been associated with OTCS or BOS with dominantly inherited de novo mutations. Whereas CD96 has been related to OTCS (one case) and to BOS (one case), ASXL1 has been related to BOS only (several cases). In this study we analyze CD96 and ASXL1 in a group of 11 affected individuals, including 2 sibs, 10 of them were diagnosed with OTCS, and one had a BOS phenotype. Exome sequences were available on six patients with OTCS and three parent pairs. Thus, we could analyze the CD96 and ASXL1 sequences in these patients bioinformatically. Sanger sequencing of all exons of CD96 and ASXL1 was carried out in the remaining patients. Detailed scrutiny of the sequences and assessment of variants allowed us to exclude putative pathogenic and private mutations in all but one of the patients. In this patient (with BOS) we identified a de novo mutation in ASXL1 (c.2100dupT). By nature and location within the gene, this mutation resembles those previously described in other BOS patients and we conclude that it may be responsible for the condition. Our results indicate that in 10 of 11, the disease (OTCS or BOS) cannot be explained by small changes in CD96 or ASXL1. However, the cohort is too small to make generalizations about the genetic etiology of these diseases.
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Urreizti
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Roca-Ayats
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Trepat
authors.affiliation: Department of Computational Genomics, Centro Investigación Prí, ncipe Felipe, Valencia, Spain.|BIER, CIBERER, Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-Garcia
authors.affiliation: BIER, CIBERER, Valencia, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Aleman
authors.affiliation: Istituto Genetica Medica, Università Cattolica Sacro Cuore, Policlínico A Gemelli, Roma, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Orteschi
authors.affiliation: Istituto Genetica Medica, Università Cattolica Sacro Cuore, Policlínico A Gemelli, Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marangi
authors.affiliation: Istituto Genetica Medica, Università Cattolica Sacro Cuore, Policlínico A Gemelli, Roma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.affiliation: Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: John M
authors.initials: JM
authors.lastname: Opitz
authors.affiliation: Department of Computational Genomics, Centro Investigación Prí, ncipe Felipe, Valencia, Spain.|BIER, CIBERER, Valencia, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Vilageliu
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Balcells
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000235:genetics* / Q000473:pathology; D059472:Exome / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C473949:ASXL1 protein, human; D015703:Antigens, CD; C116131:CD96 antigen; D012097:Repressor Proteins
keywords: ASXL1; Bohring-Opitz; CD96; Opitz C; developmental disease; molecular diagnosis; rare disease; trigonocephaly; whole exome sequencing