Two non-familial cases of Galloway-Mowat syndrome carrying the homozygous mutations of WDR73 and TP53RK
DOI:
https://doi.org/10.15448/1980-6108.2023.1.44296Keywords:
Galloway–Mowat syndrome, mutation, genetic syndrome.Abstract
Galloway–Mowat syndrome (GAMOS) is a rare hereditary disease manifested as a combination of nephrotic syndrome and central nervous system impairment. To date, many GAMOS cases attributed to various gene mutations have been reported such as WHAMM, NUP107, WDR73, OSGEP, and TP53RK. We detected two novel homozygous mutations of WDR73 ‘’NM_032856:c.G287A:p.R96K‘’ and TP53RK ‘’NM_033550:c.A193O:p.K65Q‘’ in two female kids of the consanguineous parents from different families using whole exome sequencing. Both patients almost manifested similar neurodegenerative phenotypes, including developmental delay, microcephaly, hypotonia, and brain atrophy on magnetic resonance imaging during infancy. WDR73-positive GAMOS case manifested a late-onset minimal nephrotic syndrome at the age 4 years while TP53RK-positive case presented nephrotic syndrome at the age 1 which progressed to steroid-resistant nephrotic syndrome due to lack of remission after 4-6 weeks of initial treatment with prednisone. Despite the brain abnormalities and the onset time difference of renal abnormalities, both patients are still alive. Given the heterogeneity of the renal phenotype among GAMOS types, accurate recognition of expanding spectrum of phenotype findings and regular renal function screening are necessary for an early diagnosis and timely treatment.
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El Younsi M., Kraoua L., Meddeb R., Ferjani M., Trabelsi M., Ouertani I. et al. WDR73-related Galloway Mowat syndrome with collapsing glomerulopathy. Eur J Med Genet. 2019;62:103550.
Mathiowetz A. J., Baple E., Russo A. J., Coulter A. M., Carrano E., Brown J. D. et al. An Amish founder mutation disrupts a PI(3)P-WHAMM-Arp2/3 complex-driven autophagosomal remodeling pathway. Mol Biol Cell. 2017;28:2492–2507.
Rosti R. O., Sotak B. N., Bielas S. L., Bhat G., Silhavy J. L., Aslanger A. D. et al. Homozygous mutation in NUP107 leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome. J Med Genet. 2017;54:399–403.
Colin E., Huynh Cong E., Mollet G., Guichet A., Gribouval O., Arrondel C. et al. Loss-of-function mutations in WDR73 are responsible for microcephaly and steroid-resistant nephrotic syndrome: Galloway-Mowat syndrome. Am J Hum Genet. 2014;95:637–648.
Ben-Omran T., Fahiminiya S., Sorfazlian N., Almuriekhi M., Nawaz Z., Nadaf J. et al. Nonsense mutation in the WDR73 gene is associated with Galloway-Mowat syndrome. J Med Genet. 2015;52:381–390.
Jinks R. N., Puffenberger E. G., Baple E., Harding B., Crino P., Fogo A. B. et al. Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73. Brain. 2015;138:2173–2190.
Latypova X., Matsumoto N., Vinceslas-Muller C., Bezieau S., Isidor B., Miyake N. Novel KCNB1 mutation associated with non-syndromic intellectual disability. J Hum Genet. 2017;62: 569–573.
Lin P. Y., Tseng M. H., Zenker M., Rao J., Hildebrandt F., Lin S. H. et al. Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype. Orphanet J. Rare Dis. 2018;13:226.
Braun D. A, Rao J., Mollet G., Schapiro D., Daugeron M. C., Tan W. et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet. 2017;49:1529-1538.
Keith J., Fabian V. A., Walsh P., Sinniah R., and Robitaille Y. Neuropathological homology in true Galloway-Mowat syndrome. J Child Neurol. 2011;26:510-517.
Hyun H. S., Kim S. H., Park E., Cho M. H., Kang H. G., Lee H. S. et al. A familial case of Galloway-Mowat syndrome due to a novel TP53RK mutation: a case report. BMC Med Genet. 2018;19:131.
Jinks R. N., Puffenberger E. G., Baple E., Harding B., Crino P., Fogo A. B. et al. Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73. Brain. 2015;138:2173–2190.
Chen Y, Yang Y, Yang Y, Rao J, Bai H. Diagnosis delay a family of Galloway-Mowat Syndrome caused by a classical splicing mutation of Lage3. BMC Nephrol. 2023;24:29.
Braun DA, Rao J, Mollet G, Schapiro D, Daugeron MC, Tan W, et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet. 2017;49(10):1529-38.
Vodopiutz J, Seidl R, Prayer D, Khan MI, Mayr JA, Streubel B, et al. WDR73 mutations cause infantile Neurodegeneration and variable glomerular kidney disease. Hum Mutat. 2015;36(11):1021-8.
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