Alport syndrome—insights from basic and clinical research

Kruegel, Jenny; Rubel, Diana; Groß, Oliver

doi:10.1038/nrneph.2012.259

Cited by 214 publications

(230 citation statements)

References 107 publications

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“…Ocular and auditory problems often accompany renal dysfunction because of the defective basement membranes in these organs. Patients with Alport nephropathy lack effective therapies beyond nonspecific blockade of the renin-angiotensin system (16). Therefore, new therapies to counteract the progression of Alport nephropathy are urgently sought.…”

Section: Anti-mir-21 Oligonucleotides Protect Against Kidney Failure mentioning

confidence: 99%

Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

Gomez¹,

MacKenna²,

Johnson³

et al. 2014

J. Clin. Invest.

349

317

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Section: Anti-mir-21 Oligonucleotides Protect Against Kidney Failure mentioning

confidence: 99%

Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

Gomez¹,

MacKenna²,

Johnson³

et al. 2014

J. Clin. Invest.

349

317

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“…Nevertheless, BFH and AS are quite distinct disorders, with BFH being characterized by isolated recurrent and persistent hematuria with normal renal function and better prognosis, while AS is characterized by hematuria, proteinuria, and progressive renal failure with or without sensorineural deafness and ocular abnormalities [Alport, 1927;Lemmink et al, 1996]. It is widely acknowledged that mutations in the COL4A5 gene result in X-linked AS, homozygous or compound heterozygous mutations in COL4A3 or COL4A4 are responsible for an autosomal recessive type of AS, whereas heterozygous mutations in COL4A3 or COL4A4 cause autosomal dominant AS or BFH [Slajpah et al, 2007;Kruegel et al, 2013]. Rarely, mutations in COL4A5 and COL4A6 result in X-linked AS with diffuse leiomyomatosis [Heidet et al, 1997[Heidet et al, , 1998].…”

mentioning

confidence: 99%

The COL4A3 and COL4A4 Digenic Mutations in cis Result in Benign Familial Hematuria in a Large Chinese Family

Cui

et al. 2018

Cytogenet Genome Res

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Mutations in the COL4A5 gene result in X-linked Alport syndrome, homozygous or compound heterozygous mutations in COL4A3 or COL4A4 are responsible for autosomal recessive Alport syndrome, and heterozygous mutations in COL4A3 or COL4A4 cause autosomal dominant Alport syndrome or benign familial hematuria. Recently, the existence of a digenic inheritance in Alport syndrome has been demonstrated. We here report heterozygous COL4A3 and COL4A4 digenic mutations in cis responsible for benign familial hematuria. Using bioinformatics analyses and pedigree verification, we showed that COL4A4 c.1471C>T and COL4A3 c.3418 + 1G>T variants in cis are pathogenic and co-segregate with the benign familial hematuria. This result suggests that COL4A3 and COL4A4 digenic mutations in cis mimicking an autosomal dominant inheritance should be considered as a novel inheritance pattern of benign familial hematuria, although the disease-causing mechanism remains unknown.

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“…In patients with ADAS, typical pathological changes of GBM include lamellation, splitting, thinning, or thickening [Kruegel et al, 2013;Liu et al, 2017]. However, TBMN is characterized by diffuse thin basement membrane changes [Savige et al, 2001].…”

Section: Discussionmentioning

confidence: 99%

Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes

Gao²,

Cui³

et al. 2018

Cytogenet Genome Res

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Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, and FSGS. Using bioinformatics analyses and pedigree verification, we show that these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS. Furthermore, we found that the collagen type IV-associated kidney disease phenotypes are heterogeneous, with overlapping pathology and genetic mutations. We propose that COL4A4-associated TBMN, ADAS, and FSGS should be considered as collagen type IV kidney disease subtypes that represent different phases of disease progression.

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Alport syndrome—insights from basic and clinical research

Cited by 214 publications

References 107 publications

Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

The<b><i> COL4A3</i></b> and <b><i>COL4A4</i></b> Digenic Mutations in cis Result in Benign Familial Hematuria in a Large Chinese Family

Three Novel Heterozygous<b><i> COL4A4</i></b> Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes

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