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Case Reports
. 2023 Feb 8;24(1):29.
doi: 10.1186/s12882-022-03000-5.

Diagnosis delay a family of Galloway-Mowat Syndrome caused by a classical splicing mutation of Lage3

Yan Chen  1   2   3 , Yan Yang  1   2   3 , Yang Yang  1   2   3 , Jia Rao  4 , Haitao Bai  5   6   7
Affiliations
Case Reports

Diagnosis delay a family of Galloway-Mowat Syndrome caused by a classical splicing mutation of Lage3

Yan Chen et al. BMC Nephrol. .

Abstract

Background: 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.

Case presentation: We present the clinical and genetic features of a two-year-old boy with early nephrotic syndrome, microcephaly, growth retardation hypotonia and hypothyroidism. Genetic testing showed the presence of a canonical-splice mutation in the LAGE3 gene (NM_006014: c.188 + 1C > T). A total of nine female members of the family carried the variant. 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. The overall symptoms of the disease due to the LAGE3 mutation were mild compared to other pathogenic genes.

Conclusion: As far as we know, this is the largest family case of GAMOS2 caused by LAGE3 mutation found so far. We also compared other subtypes of GAMOS. Due to the heterogeneity of the renal phenotype, regular proteinuria screening is recommended for all patients diagnosed with GAMOS.

Keywords: Early-onset nephrotic syndrome; Focal segmental glomerulosclerosis; Galloway-Mowat syndrome; LAGE3 gene; Steroid-resistant nephrotic syndrome.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The image of the proband. A and B The forehead of the proband is narrow and inclined. C All fingers are short and stubby. There are simian lines on both hands
Fig. 2
Fig. 2
The image of renal biopsy from the proband. A PASM staining. B MASSON staining glomerular sclerosis. C Foot process fusion under electron microscope)
Fig. 3
Fig. 3
Schematic diagram of LAGE3 gene structure and protein domain
Fig. 4
Fig. 4
The pedigree of a family with Gallowy-Mowat syndrome caused by splicing mutation of LAGE3. formula image indicates female members carrying LAGE3 mutation sites; formula image indicates as probands
See this image and copyright information in PMC

References

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Publication types

Supplementary concepts