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Galloway-Mowat syndrome

Galloway-Mowat Syndrome Manual Deep-Research Note

2026-04-14
Manual MONDO:0009627 Model: n/a 13 citations

Galloway-Mowat Syndrome Manual Deep-Research Note

Scope

  • Parent disease term: MONDO:0009627 Galloway-Mowat syndrome
  • Curation frame: syndrome-level parent/root, not a single-gene disorder
  • Primary convergent outcomes: early-onset nephrotic syndrome/proteinuria plus microcephaly and brain malformation
  • Key subtype families supported in the literature:
  • WDR73
  • KEOPS / t6A biogenesis: LAGE3, OSGEP, TP53RK, TPRKB, GON7, YRDC
  • nucleoporins: NUP107, NUP133
  • additional broadened genes: WDR4, PRDM15

Exact Quoted Support

Core syndrome definition

  • PMID:40533795

    Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive genetic disorder that is underrecognized.

  • PMID:40533795

    The phenotype is heterogeneous, but it is now widely accepted that early-onset nephrotic syndrome (SRNS) and microcephaly with brain malformation are characteristic features of Galloway-Mowat syndrome.

  • PMID:36755238

    Galloway-Mowat syndrome (GAMOS) is a group of rare hereditary diseases by the combination of early onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73, LAGE3, OSGEP, TP53RK, TPRKB, GON7, WDR4 or NUP133 mutations.

WDR73 subtype

  • PMID:25466283

    Galloway-Mowat syndrome is a rare autosomal-recessive condition characterized by nephrotic syndrome associated with microcephaly and neurological impairment.

  • PMID:25466283

    These data suggest that WDR73 plays a crucial role in the maintenance of cell architecture and cell survival.

  • PMID:25466283

    Altogether, WDR73 mutations cause Galloway-Mowat syndrome in a particular subset of individuals presenting with late-onset nephrotic syndrome, postnatal microcephaly, severe intellectual disability, and homogenous brain MRI features.

KEOPS / t6A pathway

  • PMID:31481669

    We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly.

  • PMID:31481669

    Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease.

  • PMID:31481669

    mutations which alter t6A biosynthesis in human cells have an impact on cell survival through decreased proliferation and protein synthesis, ultimately leading to apoptosis.

OSGEP clinical severity

  • PMID:30558655

    Overall, 6 patients from 5 different Taiwanese families were included in our study; the patients had an identical OSGEP gene mutation (c.740G > A transition) and all exhibited a uniform clinical phenotype with early-onset nephrotic syndrome, craniofacial and skeletal dysmorphism, primary microcephaly with pachygyria, and death before 2 years of age.

  • PMID:30558655

    Neurological findings consisted of microcephaly, hypotonia, developmental delay, and seizures.

  • PMID:30558655

    Brain imaging studies all showed pachygyria and hypomyelination.

  • PMID:30558655

    All patients developed early-onset nephrotic syndrome. The proteinuria was steroid-resistant and eventually resulted in renal function impairment.

  • PMID:30975089

    These two cases, in conjunction with the findings of a literature review, indicate that OSGEP pathogenic variants are associated with an earlier onset of nephrotic syndrome and shorter life expectancy than WDR73 pathogenic variants.

LAGE3 subtype and inheritance nuance

  • PMID:36755238

    Seven male members died prematurely, and three of them suffered from nephrotic syndrome, which is consistent with the x-linked gene map of the disease.

  • PMID:36755238

    The overall symptoms of the disease due to the LAGE3 mutation were mild compared to other pathogenic genes.

  • PMID:36755238

    Due to the heterogeneity of the renal phenotype, regular proteinuria screening is recommended for all patients diagnosed with GAMOS.

Nucleoporin subtypes

  • PMID:28280135

    The founder mutation was associated with concomitant reduction in NUP107 protein and in the obligate binding partner NUP133 protein, as well as density of nuclear pores in patient cells.

  • PMID:28280135

    With the addition of these individuals, we implicate an allele-specific critical role for NUP107 in the regulation of brain growth and a GAMOS-like presentation.

  • PMID:30427554

    NUP107 and NUP133 (nucleoporin 133kDa) are interacting subunits of the nuclear pore complex in the nuclear envelope during interphase, and these proteins are also involved in centrosome positioning and spindle assembly during mitosis.

  • PMID:30427554

    A nup133-knockdown zebrafish model exhibited microcephaly, fewer neuronal cells, underdeveloped glomeruli, and fusion of the foot processes of the podocytes, which mimicked human GAMOS features.

  • PMID:30427554

    These data indicate that the biallelic NUP133 loss-of-function mutation causes GAMOS.

Podocyte pathology

  • PMID:11793093

    Synaptopodin, GLEPP1, and nephrin expression was present, although reduced in Galloway-Mowat syndrome.

  • PMID:36290302

    our study indicated that nephrotic syndrome in GAMOS1 is associated with disruption of FA caused by WDR73 deficiency.

Expanded gene space

  • PMID:40533795

    Although the five subunits that encode the KEOPS complex, OSGEP/TP53RK/TPRKB/LAGE3/GON7, are known to cause Galloway-Mowat syndrome, the mutation of the WDR73, WDR4, NUP107, NUP133, and PRDM15 genes can lead to Galloway-Mowat syndrome, which makes the diagnosis more challenging.

  • PMID:33593823

    Variants in PRDM15 can cause either isolated nephrotic syndrome or a GAMOS-type syndrome on an allelic basis.

  • PMID:36681682

    Patients with mutations of WDR4, a substrate adaptor of the CUL4 E3 ligase complex, develop cerebellar atrophy and gait phenotypes.

Management evidence

  • PMID:30558655

    Prenatal ultrasound findings, fetal MRI, genetic counseling, and mutation analysis may be useful for an early prenatal diagnosis.

  • PMID:31481669

    most of the individuals carrying GON7 mutations were alive at last follow-up, with either a functioning graft or with normal renal function despite a mild to heavy proteinuria

Curation Decisions

  • Parent/root framing: The parent MONDO term already has explicit subtype children (GAMOS1 through GAMOS10) and recent review evidence confirms broader genetic heterogeneity. The disorder YAML should therefore represent the syndrome as the root disease and keep gene-defined subtypes inside has_subtypes.

  • Inheritance modeling: The literature still commonly describes GAMOS as autosomal recessive, but LAGE3 creates a real X-linked branch. The YAML should therefore keep both Autosomal recessive and X-linked recessive inheritance entries, with a note explaining the spectrum.

  • Mechanism modeling: The most defensible disease graph is convergent:

  • KEOPS / YRDC / GON7 defects -> impaired tRNA modification
  • WDR73 defects -> disrupted focal adhesion, RNA processing, and cell-cycle control
  • NUP107 / NUP133 defects -> nuclear pore and spindle dysfunction

  • all of the above -> podocyte failure + impaired brain growth

  • Phenotype selection: The safest high-signal phenotype set for the initial disease-level entry is:

  • HP:0000252 Microcephaly
  • HP:0012588 Steroid-resistant nephrotic syndrome
  • HP:0001263 Global developmental delay
  • HP:0008936 Axial hypotonia
  • HP:0001250 Seizure
  • HP:0001302 Pachygyria

  • HP:0012444 Brain atrophy

  • Treatment selection: The literature supports conservative treatment assertions only:

  • MAXO:0000079 genetic counseling
  • MAXO:0010039 organ transplantation, localized to kidney, only as subtype-limited renal rescue after ESRD

Ontology Anchors Used

  • Disease:
  • MONDO:0009627 Galloway-Mowat syndrome
  • MONDO:0033005 Galloway-Mowat syndrome 1
  • MONDO:0033006 Galloway-Mowat syndrome 2, X-linked
  • MONDO:0033007 Galloway-Mowat syndrome 3
  • MONDO:0033008 Galloway-Mowat syndrome 4
  • MONDO:0033009 Galloway-Mowat syndrome 5
  • MONDO:0032691 Galloway-Mowat syndrome 6
  • MONDO:0032692 Galloway-Mowat syndrome 7
  • MONDO:0032693 Galloway-Mowat syndrome 8
  • MONDO:0030471 Galloway-Mowat syndrome 9

  • MONDO:0030476 Galloway-Mowat syndrome 10

  • Cell and anatomy terms:

  • CL:0000653 podocyte
  • CL:0000540 neuron
  • UBERON:0002113 kidney

  • UBERON:0000955 brain

  • Biological process and component terms:

  • GO:0006400 tRNA modification
  • GO:0006396 RNA processing
  • GO:0048041 focal adhesion assembly
  • GO:0044843 cell cycle G1/S phase transition
  • GO:0051225 spindle assembly

  • GO:0005643 nuclear pore

  • Treatment terms:

  • MAXO:0000079 genetic counseling
  • MAXO:0010039 organ transplantation

PMID Set Used