Limb body wall complex, amniotic band sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)?
Paul Kruszka, Annette Uwineza, Leon Mutesa, Ariel F Martinez, Yu Abe, Elaine H Zackai, Rebecca Ganetzky, Brian Chung, Roger E Stevenson, Robert S Adelstein, Xuefei Ma, James C Mullikin, Sung-Kook Hong, Maximilian Muenke
Author Information
Paul Kruszka: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
Annette Uwineza: Center for Medical Genetics, College of Medicine and Health Sciences, University of Rwanda Huye, Rwanda.
Leon Mutesa: Center for Medical Genetics, College of Medicine and Health Sciences, University of Rwanda Huye, Rwanda.
Ariel F Martinez: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
Yu Abe: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
Elaine H Zackai: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, Perelman School of Medicine of the University of Pennsylvania Philadelphia, Pennsylvania.
Rebecca Ganetzky: Division of Human Genetics, The Children's Hospital of Philadelphia, Clinical Genetics Center, Perelman School of Medicine of the University of Pennsylvania Philadelphia, Pennsylvania.
Brian Chung: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong Pokfulam, Hong Kong.
Roger E Stevenson: Greenwood Genetic Center Greenwood, South Carolina.
Robert S Adelstein: Laboratory of Molecular Cardiology, National Heart Lung and Blood Institute, National Institutes of Health Bethesda, Maryland.
Xuefei Ma: Laboratory of Molecular Cardiology, National Heart Lung and Blood Institute, National Institutes of Health Bethesda, Maryland.
James C Mullikin: Comparative Genomics Analysis Unit, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
Sung-Kook Hong: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
Maximilian Muenke: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
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.
