title: Oblique facial clefts in Johanson-Blizzard syndrome.
abstract: Johanson-Blizzard syndrome (JBS) is considered as an infrequent, but clinically easily recognizable autosomal recessive entity by the pathognomonic combination of congenital exocrine pancreatic insufficiency and hypoplastic alae nasi, in addition to other distinctive findings such as scalp defects, hypothyroidism, and rectourogenital malformations. There are few reports of patients with JBS in association with facial clefting, referring all to types 2 to 6 of Tessier's classification that can be characterized properly as oblique facial clefts (OFCs). We describe the clinical aspects in four patients with JBS and extensive OFCs. In all of them, the diagnosis of JBS was confirmed by the demonstration of homozygous or compound-heterozygous mutations in the UBR1 gene. Additionally, we review three previously reported cases of JBS with OFCs. Taking into account a number of approximately 100 individuals affected by JBS that have been published in the literature we estimate that the frequency of OFCs in JBS is between 5% and 10%. This report emphasizes that extensive OFCs may be the severe end of the spectrum of facial malformations occurring in JBS. No obvious genotype phenotype correlation could be identified within this cohort. Thus, UBR1 should be included within the list of contributory genes of OFCs, although the exact mechanism remains unknown. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Center for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics and Cytogenetic Unit, Pediatric Division, Dr. Juan I. Menchaca Civil Hospital of Guadalajara, Guadalajara, Jalisco, México.|Department of Molecular Biology and Genomics, Dr. Enrique Corona Rivera Institute of Human Genetics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico.
authors.forename: Jorge Román
authors.initials: JR
authors.lastname: Corona-Rivera
authors.affiliation: Center for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics and Cytogenetic Unit, Pediatric Division, Dr. Juan I. Menchaca Civil Hospital of Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Zapata-Aldana
authors.affiliation: Center for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics and Cytogenetic Unit, Pediatric Division, Dr. Juan I. Menchaca Civil Hospital of Guadalajara, Guadalajara, Jalisco, México.|Department of Molecular Biology and Genomics, Dr. Enrique Corona Rivera Institute of Human Genetics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico.
authors.forename: Lucina
authors.initials: L
authors.lastname: Bobadilla-Morales
authors.affiliation: Center for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics and Cytogenetic Unit, Pediatric Division, Dr. Juan I. Menchaca Civil Hospital of Guadalajara, Guadalajara, Jalisco, México.|Department of Molecular Biology and Genomics, Dr. Enrique Corona Rivera Institute of Human Genetics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Corona-Rivera
authors.affiliation: Center for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics and Cytogenetic Unit, Pediatric Division, Dr. Juan I. Menchaca Civil Hospital of Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Christian
authors.initials: C
authors.lastname: Peña-Padilla
authors.affiliation: Center for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics and Cytogenetic Unit, Pediatric Division, Dr. Juan I. Menchaca Civil Hospital of Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Solis-Hernández
authors.affiliation: Service of Pediatrics Gastroenterology, Hospital La Católica, San José, Costa Rica.
authors.forename: Celina
authors.initials: C
authors.lastname: Guzmán
authors.affiliation: Service of Endocrinology, National Childreńs Hospital, San José, Costa Rica.
authors.forename: Erick
authors.initials: E
authors.lastname: Richmond
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Zahl
authors.affiliation: Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
authors.affiliation: Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Sukalo
mesh_terms: D000483:Alleles; D001006:Anus, Imperforate / Q000175:diagnosis* / Q000235:genetics*; D002972:Cleft Palate / Q000175:diagnosis* / Q000235:genetics*; D003241:Consanguinity; D003394:Craniofacial Dysostosis / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D003952:Diagnostic Imaging; D004476:Ectodermal Dysplasia / Q000175:diagnosis* / Q000235:genetics*; D005124:Eye Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006130:Growth Disorders / Q000175:diagnosis* / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis* / Q000235:genetics*; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D007438:Introns; D008297:Male; D019767:Maxillofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D009666:Nose / Q000002:abnormalities*; D010182:Pancreatic Diseases / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: C113474:UBR1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Tessier classification; UBR1; cleft lip; cleft palate; oblique facial clefts