NME7 – Situs Inversus Totalis

In a consanguineous family under an autosomal recessive inheritance model, two siblings presented with situs inversus totalis and were found to harbor a homozygous in-frame deletion of 34 amino acids in NME7, segregating with the phenotype (PMID:27060491).

Functional studies demonstrate that Nme7 knockout mice replicate human laterality defects, exhibiting both congenital hydrocephalus and situs inversus (PMID:21562815). Further, zebrafish Nme7 crispants display ciliary dysfunction consistent with primary ciliary dyskinesia (PMID:36533556). Together, these data support a loss-of-function mechanism disrupting γ-tubulin ring complex interactions and implicate NME7 as a human laterality gene. Additional unrelated cases are needed to elevate clinical validity.

Key take-home: NME7 should be considered in genetic diagnostics for autosomal recessive situs inversus totalis.

References

• Human Mutation • 2016 • A Homozygous Nme7 Mutation Is Associated with Situs Inversus Totalis. PMID:27060491
• Naunyn-Schmiedeberg's archives of pharmacology • 2011 • Learning about the functions of NME/NM23: lessons from knockout mice to silencing strategies. PMID:21562815
• Disease Models & Mechanisms • 2022 • Variable phenotypes and penetrance between and within different zebrafish ciliary transition zone mutants. PMID:36533556

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