title: A Homozygous Nme7 Mutation Is Associated with Situs Inversus Totalis.
abstract: We investigated the cause of situs inversus totalis (SIT) in two siblings from a consanguineous family. Genotyping and whole-exome analysis revealed a homozygous change in NME7, resulting in deletion of an exon causing an in-frame deletion of 34 amino acids located in the second NDK domain of the protein and segregated with the defective lateralization in the family. NME7 is an important developmental gene, and NME7 protein is a component of the γ-tubulin ring complex. This mutation is predicted to affect the interaction of NME7 protein with this complex as it deletes the amino acids crucial for the binding. SIT associated with homozygous deletion in our patients is in line with Nme7(-/-) mutant mice phenotypes consisting of congenital hydrocephalus and SIT, indicating a novel human laterality patterning role for NME7. Further cases are required to elaborate the full human phenotype associated with NME7 mutations.
authors.affiliation: Genetic Institute, Assaf Harofeh Medical Center, Zerifin, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Reish
authors.affiliation: Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Liam
authors.initials: L
authors.lastname: Aspit
authors.affiliation: Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Arielle
authors.initials: A
authors.lastname: Zouella
authors.affiliation: The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Otolaryngology - Head and Neck Surgery, Edith Wolfson Medical Center, Holon, Israel.
authors.forename: Yehudah
authors.initials: Y
authors.lastname: Roth
authors.affiliation: Department of Pathology, The Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Polak-Charcon
authors.affiliation: The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Pathology, The Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Baboushkin
authors.affiliation: Genetic Institute, Assaf Harofeh Medical Center, Zerifin, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Benyamini
authors.affiliation: Stephen A Wynn Institute for Vision Research and Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Scheetz
authors.affiliation: The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Pediatric Pulmunology Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
authors.forename: Huda
authors.initials: H
authors.lastname: Mussaffi
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Iowa, Iowa City, Iowa.
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.affiliation: Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Ruti
authors.initials: R
authors.lastname: Parvari
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008958:Models, Molecular; D009701:Nucleoside-Diphosphate Kinase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D000072417:Protein Domains; D017384:Sequence Deletion; D012857:Situs Inversus / Q000235:genetics*
chemical_list: D008869:Microtubule-Associated Proteins; C000595354:NME7 protein, human; D009701:Nucleoside-Diphosphate Kinase
keywords: NME7; cilia; situs inversus totalis; γ-tubulin ring complex