Mutation screening of the PCDH15 gene in Spanish patients with usher syndrome type I

Teresa Jaijo, Aki Oshima, Elena Aller, Carol Carney, Shin Ichi Usami, José M. Millán, William J. Kimberling

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: PCDH15 codes for protocadherin-15, a cell-cell adhesion protein essential in the morphogenesis and cohesion of stereocilia bundles and in the function or preservation of photoreceptor cells. Mutations in the PCDH15 gene are responsible for Usher syndrome type I (USH1F) and non-syndromic hearing loss (DFNB23). The purpose of this work was to perform PCDH15 mutation screening to identify the genetic cause of the disease in a cohort of Spanish patients with Usher syndrome type I and establish phenotype-genotype correlation. Methods: Mutation analysis of PCDH15 included additional exons recently identified and was performed by direct sequencing. The screening was performed in 19 probands with USH already screened for mutations in the most prevalent USH1 genes, myosin VIIA (MYO7A) and cadherin-23 (CDH23), and for copy number variants in PCDH15. Results: Seven different point mutations, five novel, were detected. Including the large PCDH15 rearrangements previously reported in our cohort of patients, a total of seven of 19 patients (36.8%) were carriers of at least one pathogenic allele. Thirteen out of the 38 screened alleles carried pathogenic PCDH15 variants (34.2%). Conclusions: Five out of the seven point mutations reported in the present study are novel, supporting the idea that most PCDH15 mutations are private. Furthermore, no mutational hotspots have been identified. In most patients, detected mutations led to a truncated protein, reinforcing the hypothesis that severe mutations cause the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.

Original languageEnglish (US)
Pages (from-to)1719-1726
Number of pages8
JournalMolecular Vision
Volume18
StatePublished - Jun 23 2012

Fingerprint

Usher Syndromes
Mutation
Genes
Hearing Loss
Point Mutation
Alleles
Stereocilia
Photoreceptor Cells
Inborn Genetic Diseases
Genetic Association Studies
Cadherins
Myosins
Morphogenesis
Cell Adhesion
Exons
Proteins
Phenotype

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Jaijo, T., Oshima, A., Aller, E., Carney, C., Usami, S. I., Millán, J. M., & Kimberling, W. J. (2012). Mutation screening of the PCDH15 gene in Spanish patients with usher syndrome type I. Molecular Vision, 18, 1719-1726.

Mutation screening of the PCDH15 gene in Spanish patients with usher syndrome type I. / Jaijo, Teresa; Oshima, Aki; Aller, Elena; Carney, Carol; Usami, Shin Ichi; Millán, José M.; Kimberling, William J.

In: Molecular Vision, Vol. 18, 23.06.2012, p. 1719-1726.

Research output: Contribution to journalArticle

Jaijo, T, Oshima, A, Aller, E, Carney, C, Usami, SI, Millán, JM & Kimberling, WJ 2012, 'Mutation screening of the PCDH15 gene in Spanish patients with usher syndrome type I', Molecular Vision, vol. 18, pp. 1719-1726.
Jaijo T, Oshima A, Aller E, Carney C, Usami SI, Millán JM et al. Mutation screening of the PCDH15 gene in Spanish patients with usher syndrome type I. Molecular Vision. 2012 Jun 23;18:1719-1726.
Jaijo, Teresa ; Oshima, Aki ; Aller, Elena ; Carney, Carol ; Usami, Shin Ichi ; Millán, José M. ; Kimberling, William J. / Mutation screening of the PCDH15 gene in Spanish patients with usher syndrome type I. In: Molecular Vision. 2012 ; Vol. 18. pp. 1719-1726.
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abstract = "Purpose: PCDH15 codes for protocadherin-15, a cell-cell adhesion protein essential in the morphogenesis and cohesion of stereocilia bundles and in the function or preservation of photoreceptor cells. Mutations in the PCDH15 gene are responsible for Usher syndrome type I (USH1F) and non-syndromic hearing loss (DFNB23). The purpose of this work was to perform PCDH15 mutation screening to identify the genetic cause of the disease in a cohort of Spanish patients with Usher syndrome type I and establish phenotype-genotype correlation. Methods: Mutation analysis of PCDH15 included additional exons recently identified and was performed by direct sequencing. The screening was performed in 19 probands with USH already screened for mutations in the most prevalent USH1 genes, myosin VIIA (MYO7A) and cadherin-23 (CDH23), and for copy number variants in PCDH15. Results: Seven different point mutations, five novel, were detected. Including the large PCDH15 rearrangements previously reported in our cohort of patients, a total of seven of 19 patients (36.8{\%}) were carriers of at least one pathogenic allele. Thirteen out of the 38 screened alleles carried pathogenic PCDH15 variants (34.2{\%}). Conclusions: Five out of the seven point mutations reported in the present study are novel, supporting the idea that most PCDH15 mutations are private. Furthermore, no mutational hotspots have been identified. In most patients, detected mutations led to a truncated protein, reinforcing the hypothesis that severe mutations cause the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.",
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