Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane
IntroductionWilson's disease is an autosomal recessive disorder caused by ATP7B pathogenic mutations. The hallmark of this disorder mainly consists of liver involvement, neurologic dysfunction and psychiatric features. In addition, the kidneys can also be affected by excessive copper deposition...
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Frontiers Media S.A.
2023-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1231605/full |
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| author | Hongliang Xu Hanyu Lv Xin Chen Yajun Lian Guolan Xing Yingzi Wang Ruimin Hu |
| author_facet | Hongliang Xu Hanyu Lv Xin Chen Yajun Lian Guolan Xing Yingzi Wang Ruimin Hu |
| author_sort | Hongliang Xu |
| collection | DOAJ |
| description | IntroductionWilson's disease is an autosomal recessive disorder caused by ATP7B pathogenic mutations. The hallmark of this disorder mainly consists of liver involvement, neurologic dysfunction and psychiatric features. In addition, the kidneys can also be affected by excessive copper deposition.MethodsA total of 34 patients clinically diagnosed with WD were recruited. They underwent ATP7B gene sequencing and clinical data of symptoms, examination, and treatment were collected. Moreover, renal pathology information was also investigated.ResultsWe identified 25 potentially pathogenic ATP7B variants (16 missense, 5 frameshift, 3 splicing variants and 1 large deletion mutation) in these 34 WD patients, 5 of which were novel. In our cases, the most frequent variant was c.2333G>T (R778L, 39.06%, exon 8), followed by c.2621C>T (A874V, 10.94%, exon 11) and c.3316G>A (V1106I, 7.81%, exon 11). Furthermore, we described the thinning of the glomerular basement membrane as a rare pathologically damaging feature of Wilson's disease for the first time. Additionally, two patients who received liver transplant were observed with good prognosis in present study.DiscussionOur work expanded the spectrum of ATP7B variants and presented rare renal pathological feature in WD patients, which may facilitate the development of early diagnosis, counseling, treatment regimens of WD. |
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| language | English |
| last_indexed | 2024-03-11T23:10:49Z |
| publishDate | 2023-08-01 |
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| spelling | doaj.art-acd4c853269a426fbf5f0ff7ca90954d2023-09-21T09:05:17ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-08-011410.3389/fneur.2023.12316051231605Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membraneHongliang Xu0Hanyu Lv1Xin Chen2Yajun Lian3Guolan Xing4Yingzi Wang5Ruimin Hu6Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Renal Electron Microscopy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaIntroductionWilson's disease is an autosomal recessive disorder caused by ATP7B pathogenic mutations. The hallmark of this disorder mainly consists of liver involvement, neurologic dysfunction and psychiatric features. In addition, the kidneys can also be affected by excessive copper deposition.MethodsA total of 34 patients clinically diagnosed with WD were recruited. They underwent ATP7B gene sequencing and clinical data of symptoms, examination, and treatment were collected. Moreover, renal pathology information was also investigated.ResultsWe identified 25 potentially pathogenic ATP7B variants (16 missense, 5 frameshift, 3 splicing variants and 1 large deletion mutation) in these 34 WD patients, 5 of which were novel. In our cases, the most frequent variant was c.2333G>T (R778L, 39.06%, exon 8), followed by c.2621C>T (A874V, 10.94%, exon 11) and c.3316G>A (V1106I, 7.81%, exon 11). Furthermore, we described the thinning of the glomerular basement membrane as a rare pathologically damaging feature of Wilson's disease for the first time. Additionally, two patients who received liver transplant were observed with good prognosis in present study.DiscussionOur work expanded the spectrum of ATP7B variants and presented rare renal pathological feature in WD patients, which may facilitate the development of early diagnosis, counseling, treatment regimens of WD.https://www.frontiersin.org/articles/10.3389/fneur.2023.1231605/fullWilson's diseaseATP7B genenovel mutationsrenal pathologicalliver transplantation |
| spellingShingle | Hongliang Xu Hanyu Lv Xin Chen Yajun Lian Guolan Xing Yingzi Wang Ruimin Hu Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane Frontiers in Neurology Wilson's disease ATP7B gene novel mutations renal pathological liver transplantation |
| title | Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane |
| title_full | Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane |
| title_fullStr | Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane |
| title_full_unstemmed | Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane |
| title_short | Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane |
| title_sort | novel mutations in atp7b in chinese patients with wilson s disease and identification of kidney disorder of thinning of the glomerular basement membrane |
| topic | Wilson's disease ATP7B gene novel mutations renal pathological liver transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1231605/full |
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