title: Limb body wall complex, amniotic band sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)?
abstract: Limb body wall complex (LBWC) and amniotic band sequence (ABS) are multiple congenital anomaly conditions with craniofacial, limb, and ventral wall defects. LBWC and ABS are considered separate entities by some, and a continuum of severity of the same condition by others. The etiology of LBWC/ABS remains unknown and multiple hypotheses have been proposed. One individual with features of LBWC and his unaffected parents were whole exome sequenced and Sanger sequenced as confirmation of the mutation. Functional studies were conducted using morpholino knockdown studies followed by human mRNA rescue experiments. Using whole exome sequencing, a de novo heterozygous mutation was found in the gene IQCK: c.667C>G; p.Q223E and confirmed by Sanger sequencing in an individual with LBWC. Morpholino knockdown of iqck mRNA in the zebrafish showed ventral defects including failure of ventral fin to develop and cardiac edema. Human wild-type IQCK mRNA rescued the zebrafish phenotype, whereas human p.Q223E IQCK mRNA did not, but worsened the phenotype of the morpholino knockdown zebrafish. This study supports a genetic etiology for LBWC/ABS, or potentially a new syndrome.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: Paul
authors.initials: P
authors.lastname: Kruszka
authors.affiliation: Center for Medical Genetics, College of Medicine and Health Sciences, University of Rwanda Huye, Rwanda.
authors.forename: Annette
authors.initials: A
authors.lastname: Uwineza
authors.affiliation: Center for Medical Genetics, College of Medicine and Health Sciences, University of Rwanda Huye, Rwanda.
authors.forename: Leon
authors.initials: L
authors.lastname: Mutesa
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: Ariel F
authors.initials: AF
authors.lastname: Martinez
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: Yu
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, Perelman School of Medicine of the University of Pennsylvania Philadelphia, Pennsylvania.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, Perelman School of Medicine of the University of Pennsylvania Philadelphia, Pennsylvania.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ganetzky
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong Pokfulam, Hong Kong.
authors.forename: Brian
authors.initials: B
authors.lastname: Chung
authors.affiliation: Greenwood Genetic Center Greenwood, South Carolina.
authors.forename: Roger E
authors.initials: RE
authors.lastname: Stevenson
authors.affiliation: Laboratory of Molecular Cardiology, National Heart Lung and Blood Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.affiliation: Laboratory of Molecular Cardiology, National Heart Lung and Blood Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Comparative Genomics Analysis Unit, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: Sung-Kook
authors.initials: SK
authors.lastname: Hong
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
keywords: Amniotic bands; ectopia cordis; limb anomalies; ventral midline defect