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A Homozygous Nme7 Mutation Is Associated with Situs Inversus Totalis
Journal article   Open access   Peer reviewed

A Homozygous Nme7 Mutation Is Associated with Situs Inversus Totalis

Orit Reish, Liam Aspit, Arielle Zouella, Yehudah Roth, Sylvie Polak-Charcon, Tatiana Baboushkin, Lilach Benyamini, Todd E Scheetz, Huda Mussaffi, Val C Sheffield, …
Human mutation, Vol.37(8), pp.727-731
08/2016
DOI: 10.1002/humu.22998
PMCID: PMC6066188
PMID: 27060491
url
https://doi.org/10.1002/humu.22998View
Published (Version of record) Open Access

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.
Amino Acid Sequence Sequence Deletion Microtubule-Associated Proteins - metabolism Humans Nucleoside-Diphosphate Kinase - metabolism Models, Molecular Male Nucleoside-Diphosphate Kinase - chemistry Pedigree Protein Domains Female Situs Inversus - genetics Nucleoside-Diphosphate Kinase - genetics

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