Galloway-Mowat Syndrome (GAMOS) Panel

Galloway-Mowat syndrome (GAMOS) is an extremely rare autosomal recessive disorder characterized by neurological impairments, developmental abnormalities and early-onset nephrotic syndrome (Colin et al. 2014. PubMed ID: 25466283; Jinks et al. 2015. PubMed ID: 26070982). The primary features are infantile onset of cerebellar atrophy, microcephaly and proteinuria.

Other features include, but are not limited to, hiatal hernia, seizures, dystonia, generalized hypotonia, and visual impairment. These features are variable among patients, and have overlapping presentations with other disorders. Genetic testing is essential for differential diagnosis.

Galloway-Mowat syndrome represents a clinically and genetically heterogeneous group of autosomal recessive disorders, with the exception of Galloway-Mowat syndrome 2, which is inherited in an X-linked manner. To date, ten genes have been associated with Galloway-Mowat syndrome: WDR73, NUP107, NUP133, WDR4, TPRKB, OSGEP, TP53RK, LAGE3, GON7, and YRDC (Colin et al. 2014. PubMed ID: 25466283; Jinks et al. 2015. PubMed ID: 26070982; Braun et al. 2017. PubMed ID: 28805828; Braun et al. 2018. PubMed ID: 30179222; Braun et al. 2018. PubMed ID: 30079490; Arrondel et al. 2019. PubMed ID: 31481669). LAGE3 is the X-linked gene. Pathogenic variants in these ten genes consist of missense, splicing, and small deletion/duplication variants. Large deletions and duplications have not been reported in these genes. De novo variants are rare in these genes.

WDR73 plays a role in the regulation of the microtubule network that is crucial for the development of brain and kidney.

TPRKB, OSGEP, TP53RK, LAGE3 and GON7 encode the subunits of the highly conserved KEOPS complex (Kinase, Endopeptidase and Other Proteins of small Size), which is essential for a universal chemical modification of tRNAs. YRDC is one of acting enzymes that is used in this modification pathway. WDR4 is another tRNA- modifying enzyme.

NUP107 and NUP133 encode components of the outer rings of the nuclear pore complex (NPC), which ensures proper exchange of components between the nucleus and cytoplasm.

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Since Galloway-Mowat syndrome is rare and only limited cases have been reported in each study, the clinical sensitivity of this panel is difficult to estimate. Defects in WDR73, OSGEP and NUP107 account for ~70% of documented pathogenic variants for this disorder in the Human Gene Mutation Database (HGMD).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).