Limb body wall complex, amniotic band sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)?. Issue 5 (6th May 2015)

• Record Type: Journal Article
• Authors: Kruszka, Paul; Uwineza, Annette; Mutesa, Leon; Martinez, Ariel F.; Abe, Yu; Zackai, Elaine H.; Ganetzky, Rebecca; Chung, Brian; Stevenson, Roger E.; Adelstein, Robert S.; Ma, Xuefei; Mullikin, James C.; Hong, Sung‐Kook; Muenke, Maximilian
• Is Part Of: Molecular genetics & genomic medicine. Volume 3:Issue 5(2015:Sep.)
• Page Start: 424
• Page End: 432
• Publication Date: 2015-05-06
• Subjects: Amniotic bands -- ectopia cordis -- limb anomalies -- ventral midline defect; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.153
• Languages: English
• ISSNs: 2324-9269

Abstract

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. Abstract : We present the first genetic characterization of an individual who has elements of both limb body wall complex (LBWC) and amniotic band sequence (ABS), but may also be a new syndrome. Both LBWC and ABS do not have a known genetic etiology, and there has been much debate on whether these two conditions are the same or separate entities. Using whole exome sequencing, we have found a genetic mutation in the gene IQ motif containing K ( IQCK ), which has not been previously reported in the medical literature. Using functional studies in the zebrafish, we have confirmed IQCK as the causative gene.