Renal, auricular, and ocular outcomes of Alport syndrome and their current management

Zhang, Yanqin; Ding, Jie

doi:10.1007/s00467-017-3784-3

Cited by 19 publications

(27 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Clinically, most (81%) of patients with Alport syndrome have hematuria with or without proteinuria [7] and 11% patients have proteinuria alone; the proteinuria was also seen in the present canine case. However, the glomerular lesions were focal and modest in the present case without relevance to renal lesions in human Alport syndrome [14,15]. Patients with sporadic esophageal leiomyomatosis, without personal or familial history of Alport syndrome, are reported not to have renal disorders [5,11].…”

contrasting

confidence: 56%

“…In patients with Alport syndrome, clinical findings are mainly associated with renal disorder and auditory disturbance due to abnormality in collagen generation [10,13]. Irregular thickening of the lamina densa of the glomerular basement membrane, confirmed with electron microscope, is an important diagnostic criterion [10,15]. Clinically, most (81%) of patients with Alport syndrome have hematuria with or without proteinuria [7] and 11% patients have proteinuria alone; the proteinuria was also seen in the present canine case.…”

supporting

confidence: 55%

See 1 more Smart Citation

Diffuse leiomyomatosis with circumferential thickening of the gastrointestinal wall, resembling human diffuse leiomyomatosis, in a young miniature dachshund

Kuramochi

Izawa

Mori

et al. 2020

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

Leiomyoma is the most common mesenchymal tumor in the gastrointestinal (GI) tract. Leiomyomas usually have a single or multinodular mass of various sizes, and affected animals can develop alimentary symptoms depending on the location and size. A 3-year old female miniature dachshund died after a history of refractory rectal prolapse, esophagectasis and aspiration pneumonia. At necropsy, the GI wall at the gastroesophageal and anorectal junctions was circumferentially thickened. Histologically, both GI lesions were composed of bundles of well-differentiated smooth muscles without mass formation or invasive growth. The neoplastic cells had little cellular atypia and low proliferative activity, and were positive for α-smooth muscle actin. The lesions were diagnosed as diffuse leiomyomatosis with circumferential thickening of the GI wall and has not been described in the veterinary literature.

show abstract

contrasting

confidence: 56%

supporting

confidence: 55%

Diffuse leiomyomatosis with circumferential thickening of the gastrointestinal wall, resembling human diffuse leiomyomatosis, in a young miniature dachshund

Kuramochi

Izawa

Mori

et al. 2020

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

show abstract

“…Alport syndrome (AS) is an inherited renal disease characterized by hematuria, proteinuria, and progressive renal failure, variably associated with hearing loss and ocular abnormalities [1][2][3]. It is caused by mutations in the COL4A3, COL4A4, or COL4A5 genes encoding α3, α4, and α5 chains of collagen type IV, a component of the glomerular basement membrane (GBM) in the kidney [4,5].…”

Section: Introductionmentioning

confidence: 99%

Reassessing the pathogenicity of c.2858G>T(p.(G953V)) in COL4A5 Gene: report of 19 Chinese families

et al. 2019

Self Cite

View full text Add to dashboard Cite

X-linked Alport syndrome (XLAS) is an inherited renal disease caused by mutations in COL4A5 gene. The c.2858G>T(p. (G953V)) in COL4A5 gene (rs78972735) has been considered pathogenic previously. However, there are conflicting interpretations of its pathogenicity recently. Here we presented 19 Chinese families, out of which 36 individuals (18 probands and 18 family members) carried the c.2858G>T(p.(G953V)) in COL4A5 gene. The clinical manifestations and genetic findings of them were analyzed. We found there were no clinical features of Alport syndrome not only in six probands with c.2858G>T(p.(G953V)) in COL4A5 plus pathogenic variants in other genes (e.g., WT1, ADCK4, NPHP1, TRPC6, COL4A4, and PAX2) but also in another six probands with only the c.2858G>T(p.(G953V)) variant. The other six probands with a combination of c.2858G>T(p.(G953V)) and another pathogenic variant in COL4A5 had XLAS. Eleven family members (11/18, nine females and two males) who had only the c.2858G>T(p.(G953V)) variant were asymptomatic. These two males (at age of 42 and 35 years) had normal result of urine analysis and no more clinical traits of Alport syndrome. We conclude c.2858G>T(p.(G953V)) in COL4A5 gene is not a pathogenic variant for XLAS. Individuals should not be diagnosed as XLAS only based on the detection of c.2858G>T(p.(G953V)) in COL4A5 gene.

show abstract

“…Alport syndrome is a hereditary renal disease characterized by hematuria, proteinuria, progressive renal failure, and frequently with hearing loss or ocular abnormalities. The typical ultrastructural changes of kidney in Alport syndrome are diffuse glomerular basement membrane (GBM) lamellation (Flinter, ; Kashtan, ; Zhang & Ding, ). Alport syndrome is caused by mutations in the COL4A3 (OMIM, # 120070), COL4A4 (OMIM, # 120131), or COL4A5 (OMIM, # 303630) genes encoding collagen IVα3, α4, and α5 chains (Barker et al, ; Gross, ; Mochizuki et al, ).…”

Section: Introductionmentioning

confidence: 99%

Effect of heterozygous pathogenic COL4A3 or COL4A4 variants on patients with X‐linked Alport syndrome

Zhang

Ding

Zhang

et al. 2019

Molec Gen & Gen Med

Self Cite

View full text Add to dashboard Cite

Background Alport syndrome is an inherited renal disease caused by mutations in COL4A3 , COL4A4, or COL4A5 genes. Coexisting mutations in either two of the three genes in Alport patients have been reported recently. However, the effect of heterozygous mutations in COL4A3 or COL4A4 genes in X‐linked Alport syndrome (XLAS) patients is unclear. Methods Using targeted next‐generation sequencing, six unrelated Chinese children were identified to have a combination of a pathogenic variant in COL4A5 and a heterozygous mutation in COL4A3 or COL4A4 . They were three males and three females. Another three XLAS males each with only one pathogenic variant in COL4A5 were included. The clinical data were analyzed and compared between the males in two groups (group 1, males with a pathogenic variant in COL4A5 and a heterozygous pathogenic variant in COL4A3 or COL4A4 ; group 2, males with only one pathogenic variant in COL4A5 ). Results Patients with XLAS who also had heterozygous pathogenic COL4A3 or COL4A4 variants accounted for 1% of Alport syndrome. In this study, three children showed coexisting pathogenic variants in COL4A5 and COL4A3 . Two children showed pathogenic variants in COL4A5 and COL4A4 . One child had pathogenic variants in the three COL4A3‐5 genes, in which the pathogenic variant in COL4A5 was de novo and the pathogenic variants in COL4A4 and COL4A3 were inherited independently (in trans). The site and type of mutations in COL4A5 were similar between the two groups. It was revealed that males in group 1 presented more severe proteinuria than males in group 2 ( p < 0.05 ). Conclusion The present study provides further evidence for complicated genotype in Alport syndrome. For the first time, we reported a case with three pathogenic variants in COL4A5 , COL4A3 , and COL4A4 genes. Moreover, we found that heterozygous pathogenic COL4A3 or COL4A4 variants are likely to make XLAS disease more serious.

show abstract

Renal, auricular, and ocular outcomes of Alport syndrome and their current management

Cited by 19 publications

References 53 publications

Diffuse leiomyomatosis with circumferential thickening of the gastrointestinal wall, resembling human diffuse leiomyomatosis, in a young miniature dachshund

Diffuse leiomyomatosis with circumferential thickening of the gastrointestinal wall, resembling human diffuse leiomyomatosis, in a young miniature dachshund

Reassessing the pathogenicity of c.2858G>T(p.(G953V)) in COL4A5 Gene: report of 19 Chinese families

Effect of heterozygous pathogenic COL4A3 or COL4A4 variants on patients with X‐linked Alport syndrome

Contact Info

Product

Resources

About