• ovarian dysgenesis 6

This report describes ovarian dysgenesis 6 (ODG6); ODG6 exhibits autosomal recessive inheritance. In an investigation of a family with multiple cases of XX gonadal dysgenesis, a missense variant in the human gene NUP107 was identified as a candidate causative mutation. NUP107 encodes a component of the nuclear pore complex. There is a single orthologous gene in Drosophila, Dmel\Nup107, for which an amorphic allele resulting from imprecise excision of an insertion, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated. The human NUP107 gene has also been implicated in nephrotic syndrome 11 (MIM:616730).

The human NUP107 gene has not been introduced into flies.

An amorphic mutation of Dmel\Nup107 is lethal. Nup107 knockdown in somatic gonadal cells results in female sterility; males are fertile. Introduction of constructs carrying the wild-type fly gene or one carrying a mutation analogous to the missense mutation implicated in 46,XX gonadal dysgenesis in human were assessed for capacity to rescue the amorphic phenotype. Both constructs rescued the lethality phenotype and resulted in adults with no conspicuous morphological defects. However, the females carrying the construct with missense mutation exhibited significantly reduced fertility compared to those carrying the wild-type construct. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): D364N in the fly Nup107 gene (corresponds to D447N in the human NUP107 gene).

Work in flies on repair of heterochromatic double strand breaks (DSBs) suggests that relocalization of the regions of the DSBs to the nuclear periphery occurs during repair; components of the nuclear pore complex, including the Nup107 protein, play a role in this process. Animals heterozygous for a putative amorphic mutation of Dmel\Nup107 exhibit significant genome instability in larval neuroblasts, including aneuploidy, chromosome fusions and changes in the number of satellites; (this allele is homozygous lethal). A small number of physical interactions have been described for Dmel\Nup107; see below and in the Nup107 gene report.

For fly transgenic constructs and classical alleles, detailed phenotypic descriptions can be found in the allele reports; allele reports can be accessed from the gene report or by clicking on the allele symbols in the Disease Ontology and Reagent tables below.

[updated Sep. 2018 by FlyBase; FBrf0222196]