title: Identification of a novel CNTNAP1 mutation causing arthrogryposis multiplex congenita with cerebral and cerebellar atrophy.
abstract: Arthrogryposis multiplex congenital, the occurrence of multiple joint contractures at birth, can in some cases be accompanied by insufficient myelination of peripheral nerves, muscular hypotonia, reduced tendon reflexes, and respiratory insufficiency. Recently mutations in the CASPR/CNTN1 complex have been associated with similar severe phenotypes and CNTNAP1 gene mutations, causing loss of the CASPR protein, were shown to cause severe, prenatal onset arthrogryposis multiplex congenita in four unrelated families. Here we report a consanguineous Arab family from Qatar with three children having an early lethal form of arthrogryposis multiplex congenita and a novel frameshift mutation in CNTNAP1. We further expand the existing CNTNAP1-associated phenotype to include profound cerebral and cerebellar atrophy.
authors.affiliation: Section of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Qatar.
authors.forename: Shenela
authors.initials: S
authors.lastname: Lakhani
authors.affiliation: Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Boston, MA, 02115, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Doan
authors.affiliation: Section of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Qatar.
authors.forename: Mariam
authors.initials: M
authors.lastname: Almureikhi
authors.affiliation: Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Boston, MA, 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, 02115, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, 02115, USA.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Partlow
authors.affiliation: Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Boston, MA, 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, 02115, USA; Department of Pediatrics, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors.forename: Muna
authors.initials: M
authors.lastname: Al Saffar
authors.affiliation: Section of Neurology, Department of Pediatrics, Hamad Medical Corporation, Qatar.
authors.forename: Mahmoud F
authors.initials: MF
authors.lastname: Elsaid
authors.affiliation: Section of Children Development and Rehabilitation, Department of Pediatrics, Hamad Medical Corporation, Qatar.
authors.forename: Nada
authors.initials: N
authors.lastname: Alaaraj
authors.affiliation: Pediatric Neuroradiology, Department of Neuroradiology, University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: A
authors.initials: A
authors.lastname: James Barkovich
authors.affiliation: Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Boston, MA, 02115, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, 02115, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, 02115, USA; Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
authors.affiliation: Section of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Qatar. Electronic address: tawben11@hotmail.com.
authors.forename: Tawfeg
authors.initials: T
authors.lastname: Ben-Omran
mesh_terms: D001176:Arthrogryposis / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree
chemical_list: C491323:CNTNAP1 protein, human; D015816:Cell Adhesion Molecules, Neuronal
keywords: Arab; Arthrogryposis multiplex congenita; CNTNAP1; Cerebral atrophy; Qatar