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Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa.

Huang Y, Zhang J, Li C, Yang G, Liu M, Wang QK, Tang Z - BMC Med. Genet. (2010)

Bottom Line: This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids.Our study represents the first independent confirmation that mutations in EYS cause arRP.Additionally, this is the first EYS mutation identified in the Chinese population.

View Article: PubMed Central - HTML - PubMed

Affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

ABSTRACT

Background: Retinitis pigmentosa is the most important hereditary retinal degenerative disease, which has a high degree of clinical and genetic heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal recessive (arRP), but the gene(s) causing arRP in most families has yet to be identified. The purpose of this study is to identify the genetic basis of severe arRP in a consanguineous Chinese family.

Methods: Linkage and haplotype analyses were used to define the chromosomal location of the pathogenic gene in the Chinese arRP family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of EYS was used to determine the disease-causing mutation, and to demonstrate that the mutation co-segregates with the disease in the family.

Results: A single nucleotide substitution of G to T at nucleotide 5506 of EYS was identified in the Chinese arRP family. This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids. Three affected siblings in the family were homozygous for the p.E1836X mutation, while the other unaffected family members carried one mutant allele and one normal EYS allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal controls.

Conclusions: The EYS gene is a recently identified disease-causing gene for retinitis pigmentosa, and encodes the orthologue of Drosophila spacemaker. To date, there are only eight mutations in EYS that have been identified to cause arRP. Here we report one novel homozygous nonsense mutation of EYS in a consanguineous Chinese arRP family. Our study represents the first independent confirmation that mutations in EYS cause arRP. Additionally, this is the first EYS mutation identified in the Chinese population.

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Pedigree structure and haplotype analysis at the RP25 locus. Blackened bars indicate the disease haplotype. Filled squares or filled circles represent male or female individuals affected with RP, respectively. Arrow points to the proband (II2). All patients in the arRP family carry the homozygous haplotype between single nucleotide polymorphisms rs4710292 and rs4710437. The genomic positions of two markers are from Human (Homo sapiens) Genome Browser Gateway, the GRCh37 build version, and six SNPs are from NCBI B37.1 assembly.
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Figure 1: Pedigree structure and haplotype analysis at the RP25 locus. Blackened bars indicate the disease haplotype. Filled squares or filled circles represent male or female individuals affected with RP, respectively. Arrow points to the proband (II2). All patients in the arRP family carry the homozygous haplotype between single nucleotide polymorphisms rs4710292 and rs4710437. The genomic positions of two markers are from Human (Homo sapiens) Genome Browser Gateway, the GRCh37 build version, and six SNPs are from NCBI B37.1 assembly.

Mentions: The RP in the consanguineous Chinese family is inherited in an autosomal recessive mode (figure 1). Parents I1 and I2 are third cousins. The proband II2 and his two sisters had deteriorating vision, while the parents and young brother II4 did not show any RP features. The family history was negative for deteriorating vision or night blindness.


Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa.

Huang Y, Zhang J, Li C, Yang G, Liu M, Wang QK, Tang Z - BMC Med. Genet. (2010)

Pedigree structure and haplotype analysis at the RP25 locus. Blackened bars indicate the disease haplotype. Filled squares or filled circles represent male or female individuals affected with RP, respectively. Arrow points to the proband (II2). All patients in the arRP family carry the homozygous haplotype between single nucleotide polymorphisms rs4710292 and rs4710437. The genomic positions of two markers are from Human (Homo sapiens) Genome Browser Gateway, the GRCh37 build version, and six SNPs are from NCBI B37.1 assembly.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927534&req=5

Figure 1: Pedigree structure and haplotype analysis at the RP25 locus. Blackened bars indicate the disease haplotype. Filled squares or filled circles represent male or female individuals affected with RP, respectively. Arrow points to the proband (II2). All patients in the arRP family carry the homozygous haplotype between single nucleotide polymorphisms rs4710292 and rs4710437. The genomic positions of two markers are from Human (Homo sapiens) Genome Browser Gateway, the GRCh37 build version, and six SNPs are from NCBI B37.1 assembly.
Mentions: The RP in the consanguineous Chinese family is inherited in an autosomal recessive mode (figure 1). Parents I1 and I2 are third cousins. The proband II2 and his two sisters had deteriorating vision, while the parents and young brother II4 did not show any RP features. The family history was negative for deteriorating vision or night blindness.

Bottom Line: This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids.Our study represents the first independent confirmation that mutations in EYS cause arRP.Additionally, this is the first EYS mutation identified in the Chinese population.

View Article: PubMed Central - HTML - PubMed

Affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

ABSTRACT

Background: Retinitis pigmentosa is the most important hereditary retinal degenerative disease, which has a high degree of clinical and genetic heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal recessive (arRP), but the gene(s) causing arRP in most families has yet to be identified. The purpose of this study is to identify the genetic basis of severe arRP in a consanguineous Chinese family.

Methods: Linkage and haplotype analyses were used to define the chromosomal location of the pathogenic gene in the Chinese arRP family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of EYS was used to determine the disease-causing mutation, and to demonstrate that the mutation co-segregates with the disease in the family.

Results: A single nucleotide substitution of G to T at nucleotide 5506 of EYS was identified in the Chinese arRP family. This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids. Three affected siblings in the family were homozygous for the p.E1836X mutation, while the other unaffected family members carried one mutant allele and one normal EYS allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal controls.

Conclusions: The EYS gene is a recently identified disease-causing gene for retinitis pigmentosa, and encodes the orthologue of Drosophila spacemaker. To date, there are only eight mutations in EYS that have been identified to cause arRP. Here we report one novel homozygous nonsense mutation of EYS in a consanguineous Chinese arRP family. Our study represents the first independent confirmation that mutations in EYS cause arRP. Additionally, this is the first EYS mutation identified in the Chinese population.

Show MeSH
Related in: MedlinePlus