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

2018 ◽  
Vol 154 (3) ◽  
pp. 132-136 ◽  
Author(s):  
Ang Li ◽  
Ying-Xia Cui ◽  
Xing Lv ◽  
Jian-Hong Liu ◽  
Er-Zhi Gao ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Bioinformatics Analyses ◽  
Digenic Inheritance ◽  
Pedigree Verification ◽  
In Cis ◽  
Benign Familial Hematuria ◽  
Familial Hematuria

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.

scholarly journals Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria

2007 ◽  
Vol 71 (12) ◽  
pp. 1287-1295 ◽  
Author(s):  
M. Šlajpah ◽  
B. Gorinšek ◽  
G. Berginc ◽  
A. Vizjak ◽  
D. Ferluga ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Novel Mutations ◽  
Benign Familial Hematuria ◽  
Familial Hematuria

scholarly journals COL4A3/COL4A4 mutations: From familial hematuria to autosomal-dominant or recessive Alport syndrome

2002 ◽  
Vol 61 (6) ◽  
pp. 1947-1956 ◽  
Author(s):  
Ilaria Longo ◽  
Paola Porcedda ◽  
Francesca Mari ◽  
Daniela Giachino ◽  
Ilaria Meloni ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Familial Hematuria

scholarly journals A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jing Wu ◽  
Jun Zhang ◽  
Li Liu ◽  
Bo Zhang ◽  
Tomohiko Yamamura ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Wide Spectrum ◽  
Case Series ◽  
Pcr Analysis ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Rt Pcr ◽  
Col4a5 Gene ◽  
Minigene Assay

Abstract Background Alport syndrome (AS), which is a rare hereditary disease caused by mutations of genes including COL4A3, COL4A4 and COL4A5, has a wide spectrum of phenotypes. Most disease-causing variants of AS are located in the exons or the conservative splicing sites of these genes, while little is known about the intronic disease-causing variants. Methods A Chinese AS family was recruited in this study. All the clinical data of AS patient were collected from medical records. After pedigree analysis, the pathogenic variants were studied by the whole exome sequencing (WES). Minigene assay and in vivo RT-PCR analysis were performed to validate the functions of the variants. Results Renal biopsy showed a typical histopathology changes of AS. WES revealed compound heterozygous substitution, NM_033380 c.991–14(IVS17) A > G, in the intron 17 of the COL4A5 gene, which were confirmed by Sanger sequencing. Moreover, the variant was co-segregated with the phenotype in this family. Minigene assay in cultured cell lines showed that a splicing error was induced by this intronic variant, which further confirmed by in vivo RT-PCR analysis. Conclusion A novel intronic disease-causing variant in COL4A5 gene was identified by WES, which was the molecular pathogenic basis of AS.

scholarly journals Identification of a novel pathogenic COL4A3 gene mutation in a Chinese family with autosomal dominant Alport syndrome: A case report

2021 ◽  
Vol 15 (5) ◽  
Author(s):  
Da-An Nie ◽  
Chao-Rui Xia ◽  
Ke-Cheng Huang ◽  
Jie Liu ◽  
Ting Gan ◽  
...  
Keyword(s):  
Case Report ◽  
Gene Mutation ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Chinese Family

scholarly journals A novel compound heterozygous COL4A4 mutation in a Chinese family with Alport syndrome

Medicine ◽  
2021 ◽  
Vol 100 (47) ◽  
pp. e27890
Author(s):  
Ji-Yu Chen ◽  
Jing-Jing Cui ◽  
Xi-Ran Yang ◽  
Yan-Fang Li ◽  
Yan-Hua Zhang ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Chinese Family ◽  
Compound Heterozygous

scholarly journals Effective variant filtering and expected candidate variant yield in studies of rare human disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Brent S. Pedersen ◽  
Joe M. Brown ◽  
Harriet Dashnow ◽  
Amelia D. Wallace ◽  
Matt Velinder ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Rare Disease ◽  
Genome Sequencing ◽  
Autosomal Dominant ◽  
De Novo ◽  
Autosomal Dominant Inheritance ◽  
Compound Heterozygous ◽  
Whole Genome ◽  
Dominant Inheritance ◽  
Family Based

AbstractIn studies of families with rare disease, it is common to screen for de novo mutations, as well as recessive or dominant variants that explain the phenotype. However, the filtering strategies and software used to prioritize high-confidence variants vary from study to study. In an effort to establish recommendations for rare disease research, we explore effective guidelines for variant (SNP and INDEL) filtering and report the expected number of candidates for de novo dominant, recessive, and autosomal dominant modes of inheritance. We derived these guidelines using two large family-based cohorts that underwent whole-genome sequencing, as well as two family cohorts with whole-exome sequencing. The filters are applied to common attributes, including genotype-quality, sequencing depth, allele balance, and population allele frequency. The resulting guidelines yield ~10 candidate SNP and INDEL variants per exome, and 18 per genome for recessive and de novo dominant modes of inheritance, with substantially more candidates for autosomal dominant inheritance. For family-based, whole-genome sequencing studies, this number includes an average of three de novo, ten compound heterozygous, one autosomal recessive, four X-linked variants, and roughly 100 candidate variants following autosomal dominant inheritance. The slivar software we developed to establish and rapidly apply these filters to VCF files is available at https://github.com/brentp/slivar under an MIT license, and includes documentation and recommendations for best practices for rare disease analysis.

scholarly journals INF2 p.Arg214Cys mutation in a Chinese family with rapidly progressive renal failure and follow-up of renal transplantation: case report and literature review

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wenbo Zhao ◽  
Xinxin Ma ◽  
Xiaohao Zhang ◽  
Dan Luo ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Disease ◽  
Autosomal Dominant ◽  
Mutational Analysis ◽  
Elevated Serum ◽  
Chinese Family ◽  
Progressive Renal Failure ◽  
Rapidly Progressive Renal Failure ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Heterozygous mutations in the inverted formin 2 (INF2) gene are related to secondary focal segmental glomerulosclerosis (FSGS), a rare secondary disease associated with rapidly progressive renal failure. Case presentation We report a patient with familial autosomal INF2 mutation manifesting nephritic syndromes and elevated serum creatinine levels. Mutational analysis revealed an autosomal dominant (AD) inheritance pattern and a mutation in exon 4 (p.Arg214Cys) of INF2 as the likely cause, which has not been previously described in an Asian family. The patient progressed to end-stage renal disease (ESRD) and received hemodialysis. His mother had undergone renal transplant 3 years earlier, and his grandmother had carried the p.Arg214Cys mutation for more than 80 years without any sign of renal dysfunction. Conclusions This is the first report to identify an association between a familial autosomal dominant INF2 p.Arg214Cys mutation and rapidly progressive renal disease in an Asian family. INF2 mutation analysis should not be restricted to individuals without family history of FSGS, rather it should also be performed on individuals for whom drug-based therapies are not effective. In this case, kidney transplant is an effective alternative.

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