4.Analysis of genetic variant in a child with autosomal recessive Alport syndrome.
Lan CHEN ; Yiyan ZHANG ; Weisheng LIN
Chinese Journal of Medical Genetics 2021;38(10):947-950
OBJECTIVE:
To explore the genetic basis for a pedigree affected with Alport syndrome.
METHODS:
Next generation sequencing and Sanger sequencing was applied to detect potential variants of the COL4A3, COL4A4 and COL4A5 genes among members from the pedigree and 100 unrelated healthy controls.
RESULTS:
The proband and his twin brother were found to carry two novel variants, namely c.4953G>A and c.4623C>A, of the COL4A4 gene, which were respectively inherited from her father and mother. The same variants were not detected among the 100 healthy controls and medical literature. Based on the guidelines of the American College of Medical Genetics and Genomics, both the c.4953G>A and c.4623C>A variants were predicted to be pathogenic (PVS1+PM2_supporting+PP1).
CONCLUSION
The c.4953G>A and c.4623C>A variants of the COLA4A gene probably underlay the Alport syndrome in this pedigree. Above finding has enriched the spectrum of COLA4A gene variants.
Autoantigens/genetics*
;
Child
;
Collagen Type IV/genetics*
;
Female
;
Humans
;
Male
;
Mutation
;
Nephritis, Hereditary/genetics*
;
Pedigree
6.Prenatal gene diagnosis of Alport syndrome.
Hong-wen ZHANG ; Jie DING ; Fang WANG
Chinese Journal of Pediatrics 2007;45(9):681-683
7.Genetic and clinical analysis of a pedigree affected with X-linked dominant Alport syndrome due to a novel variant of COL4A5 gene.
Qian MA ; Jinlin WU ; Lingyi CHE ; Xiangdong KONG
Chinese Journal of Medical Genetics 2021;38(5):461-464
OBJECTIVE:
To explore the genetic basis for a Chinese pedigree affected with X-linked hereditary Alport syndrome.
METHODS:
Next generation sequencing was carried out for the pedigree. Candidate variant was validated by Sanger sequencing. Pathological changes of renal basement membrane and expression of COL4A5 protein were analyzed by renal biopsy and immunofluorescence assay, respectively.
RESULTS:
All patients from the pedigree manifested progressive renal damage, gross hematuria, proteinuria and nephrotic syndrome. Renal biopsy of the proband revealed thickening of the basement membrane. No expression of the COL4A5 gene was detected by immunofluorescence. High-throughput sequencing and Sanger sequencing indicated that the proband has carried a c.3706delC (p.1236Pfs*69) variant in exon 41 of the COL4A5 gene. The same variant was also found in his mother and two brothers whom were similarly affected.
CONCLUSION
The novel c.3706delC (p.1236Pfs*69) variant of the COL4A5 gene probably underlay the pathogenesis of X-linked hereditary Alport syndrome in this pedigree. Above findings have enriched the spectrum of COL4A5 gene variants and provided a basis for the diagnosis and genetic counseling for the pedigree.
Collagen Type IV/genetics*
;
Hematuria
;
High-Throughput Nucleotide Sequencing
;
Humans
;
Male
;
Mutation
;
Nephritis, Hereditary/genetics*
;
Pedigree
8.Analysis of Alport syndrome induced by type IV collagen alpha 5 gene mutation in two families.
Qing YE ; Yingying ZHANG ; Jingjing WANG ; Jianhua MAO
Journal of Zhejiang University. Medical sciences 2019;48(4):384-389
OBJECTIVE:
To investigate genetic characteristics of Alport syndrome.
METHODS:
High-throughput sequencing-based whole exome sequencing was performed in two patients with recurrent unexplained abnormal urinalysis. The pathogenicity of the genetic variations, type of Mendelian genetics, and clinical phenotypes were analysed, and the disease-cause mutations were confirmed in the family members using Sanger sequencing.
RESULTS:
Two heterozygous splice site mutations of gene c.2147-2A > T (IVS27) and c.646-2A > G (IVS11) (NM_033380) were found in patients of the two families, which showed a co-segregation association with the affected members of the families.
CONCLUSIONS
Alport syndrome is mainly inherited from direct female patients, and prenatal genetic screening based on amniotic fluid testing can effectively prevent birth defects in patients with a family history of this characteristic phenotype.
Collagen Type IV
;
genetics
;
Female
;
Genetic Testing
;
Humans
;
Mutation
;
Nephritis, Hereditary
;
genetics
;
Phenotype
;
Prenatal Diagnosis
9.Analysis of two Chinese pedigrees affected with Alport syndrome due to novel variants of COL4A5 gene.
Hongjun GUO ; Fengxun LIU ; Zijun YANG
Chinese Journal of Medical Genetics 2022;39(11):1224-1227
OBJECTIVE:
To explore the genetic basis for two Chinese pedigrees affected with Alport syndrome.
METHODS:
Potential variants of the COL4A5 gene were screened by next generation sequencing (NGS). Candidate variants were verified by Sanger sequencing of other members from the pedigrees as well as 100 healthy controls. ClustalX 2.1 win was used to analyze the conservation of amino acid sequences. SWISS-MODEL was used for assessing the influence of variations on the protein structure.
RESULTS:
Two heterozygous missense variants of the COL4A5 gene, namely c.2210G>A (p.Gly737Asp) and c.3799G>A (p.Gly1267Ser), were respectively identified in the affected individuals from the two pedigrees but not among the 100 healthy controls. Neither variant was reported previously.
CONCLUSION
The c.2210G>A (p.Gly737Asp) and c.3799G>A (p.Gly1267Ser) variants of the COL4A5 gene probably underlay the Alport syndrome in these pedigrees. Above finding has enriched the spectrum of COL4A5 gene variants and provided a basis for genetic counseling and prenatal diagnosis for the families.
Pregnancy
;
Female
;
Humans
;
Nephritis, Hereditary/genetics*
;
Pedigree
;
Collagen Type IV/genetics*
;
Mutation
;
China
10.Genetic analysis of a patient with Alport syndrome due to compound heterozygous variants of COL4A4 gene.
Bingbing YANG ; Fengxun LIU ; Lanlan ZOU ; Xiaoling XUE ; Jinhong MIAO
Chinese Journal of Medical Genetics 2023;40(9):1150-1154
OBJECTIVE:
To analyze the clinical phenotype and genetic characteristics of a patient with Alport syndrome.
METHODS:
A patient with Alport syndrome who had visited the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the patient were collected. High-throughput sequencing was carried out to detect potential variant of the COL4A3, COL4A4 and COL4A5 genes, and Sanger sequencing was carried out for verification of candidate variants in the family.
RESULTS:
The main clinical manifestations of the patient included hematuria, proteinuria, and impaired hearing. Audiometric testing suggested symmetrical cochlear sensory neural hearing loss on both sides. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. Genetic testing revealed that the patient has harbored compound heterozygous variants of the COL4A4 gene, namely c.940G>A (p.Gly314Ser) and c.3773G>A (p.Gly1258Asp), which were respectively inherited from her father and mother. Neither variant has been reported before, and were predicted to be pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.
CONCLUSION
The c.940G>A (p.Gly314Ser) and c.3773G>A (p.Gly1258Asp) compound heterozygous variants of the COL4A4 gene probably underlay the Alport syndrome in this patient. Above finding has enriched the mutational spectrum of the COL4A4 gene.
Female
;
Humans
;
Nephritis, Hereditary/genetics*
;
Hematuria
;
Genetic Testing
;
Genomics
;
Hearing
;
Collagen Type IV/genetics*
Result Analysis
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