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A novel COL4A5 mutation identified in a Chinese Han family using exome sequencing.

Xiu X, Yuan J, Deng X, Xiao J, Xu H, Zeng Z, Guan L, Xu F, Deng S - Biomed Res Int (2014)

Bottom Line: This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family.The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD).Our discovery broadens the mutation spectrum in the COL4A5 gene associated with AS, which may also shed new light on genetic counseling for AS.

View Article: PubMed Central - PubMed

Affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China ; Department of Pharmacy, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, Hunan 410008, China.

ABSTRACT
Alport syndrome (AS) is a monogenic disease of the basement membrane (BM), resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and ocular anomalies. It is caused by mutations in the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alpha-4 gene (COL4A4), and the collagen type IV alpha-5 gene (COL4A5), which encodes type IV collagen α3, α4, and α5 chains, respectively. To explore the disease-related gene in a four-generation Chinese Han pedigree of AS, exome sequencing was conducted on the proband, and a novel deletion mutation c.499delC (p.Pro167Glnfs*36) in the COL4A5 gene was identified. This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family. Neither sensorineural hearing loss nor typical COL4A5-related ocular abnormalities (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy) were present in patients of this family. The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD). Our discovery broadens the mutation spectrum in the COL4A5 gene associated with AS, which may also shed new light on genetic counseling for AS.

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Pedigree of the family with X-linked Alport syndrome. N: normal, M: COL4A5 c.499delC (p.Pro167Glnfs*36) mutation.
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fig1: Pedigree of the family with X-linked Alport syndrome. N: normal, M: COL4A5 c.499delC (p.Pro167Glnfs*36) mutation.

Mentions: A pedigree consisting of 10 individuals across 4 generations of Chinese Han family was enrolled in this study (Figure 1). Peripheral blood samples were collected from 6 members of this family, including 4 patients. Peripheral blood samples were also collected from 100 unrelated ethnically matched normal controls (male/female: 50/50, age 40.6 ± 8.4 years). All participants underwent clinical evaluation, auditory and typical COL4A5-related ophthalmological examinations (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy). The protocol of this study was approved by the Ethics Committee of the Third Xiangya Hospital, Central South University, and all participants signed informed consent.


A novel COL4A5 mutation identified in a Chinese Han family using exome sequencing.

Xiu X, Yuan J, Deng X, Xiao J, Xu H, Zeng Z, Guan L, Xu F, Deng S - Biomed Res Int (2014)

Pedigree of the family with X-linked Alport syndrome. N: normal, M: COL4A5 c.499delC (p.Pro167Glnfs*36) mutation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109303&req=5

fig1: Pedigree of the family with X-linked Alport syndrome. N: normal, M: COL4A5 c.499delC (p.Pro167Glnfs*36) mutation.
Mentions: A pedigree consisting of 10 individuals across 4 generations of Chinese Han family was enrolled in this study (Figure 1). Peripheral blood samples were collected from 6 members of this family, including 4 patients. Peripheral blood samples were also collected from 100 unrelated ethnically matched normal controls (male/female: 50/50, age 40.6 ± 8.4 years). All participants underwent clinical evaluation, auditory and typical COL4A5-related ophthalmological examinations (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy). The protocol of this study was approved by the Ethics Committee of the Third Xiangya Hospital, Central South University, and all participants signed informed consent.

Bottom Line: This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family.The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD).Our discovery broadens the mutation spectrum in the COL4A5 gene associated with AS, which may also shed new light on genetic counseling for AS.

View Article: PubMed Central - PubMed

Affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China ; Department of Pharmacy, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, Hunan 410008, China.

ABSTRACT
Alport syndrome (AS) is a monogenic disease of the basement membrane (BM), resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and ocular anomalies. It is caused by mutations in the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alpha-4 gene (COL4A4), and the collagen type IV alpha-5 gene (COL4A5), which encodes type IV collagen α3, α4, and α5 chains, respectively. To explore the disease-related gene in a four-generation Chinese Han pedigree of AS, exome sequencing was conducted on the proband, and a novel deletion mutation c.499delC (p.Pro167Glnfs*36) in the COL4A5 gene was identified. This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family. Neither sensorineural hearing loss nor typical COL4A5-related ocular abnormalities (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy) were present in patients of this family. The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD). Our discovery broadens the mutation spectrum in the COL4A5 gene associated with AS, which may also shed new light on genetic counseling for AS.

Show MeSH
Related in: MedlinePlus