T Jaijo

Publications (10)41.73 Total impact

• Article: Functional analysis of splicing mutations in MYO7A and USH2A genes.

  T Jaijo, E Aller, M J Aparisi, G García-García, I Hernan, M J Gamundi, C Nájera, M Carballo, J M Millán
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  ABSTRACT: Usher syndrome is defined by the association of sensorineural hearing loss, retinitis pigmentosa and variable vestibular dysfunction. Many disease-causative mutations have been identified in MYO7A and USH2A genes, which play a major role in Usher syndrome type I and type II, respectively. The pathogenic nature of mutations that lead to premature stop codons is not questioned; nevertheless, additional studies are needed to verify the pathogenicity of some changes such as those putatively involved in the splice process. Five putative splice-site variants were detected in our cohort of patients: c.2283-1G>T and c.5856G>A in MYO7A and c.1841-2A>G, c.2167+5G>A and c.5298+1G>C in the USH2A gene. In this study, we analyze these changes with bioinformatic tools and investigate the expression of MYO7A and USH2A transcripts through hybrid minigene assays. Our study showed that all five mutations abolished the consensus splice site producing the skipping of involved exons. In addition, for variant c.2167+5G>A, a new donor splice site was observed. Our data reveal the pathogenic nature of the analyzed variants. The fact that splicing mutations led to in-frame or out-of-frame alterations cannot explain phenotypic differences, thus, genotype-phenotype correlations cannot be inferred.
  Clinical Genetics 04/2010; 79(3):282-8. · 3.13 Impact Factor
• Article: [Genetic counselling in visual and auditory disorders].

  J M Millán, E Aller, T Jaijo, E Grau, M Beneyto, C Nájera
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  ABSTRACT: Inherited retinal dystrophies and hearing loss disorders have a broad clinical and genetic heterogeneity. Over the last decade there have been major advances in our understanding of the molecular pathology of these diseases; currently over 200 genes and loci are known to be involved in retinal disorders, and over 60 genes/loci are causative for hearing impairment. Genetic testing is crucial for confirming the diagnosis at a molecular level. It also allows a more precise prognosis to be made of the future clinical evolution, as well as an accurate genetic and reproductive counselling, and raises the possibility of creating genetically homogeneous groups of patients for future clinical trials. The high number of genes responsible for these disorders makes molecular testing overwhelming in terms of cost, time and technical effectiveness, and no centre offers testing of all known genes. Several diagnostic tools have emerged recently to circumvent this problem. In this report, we review the vast genetic heterogeneity of retinal dystrophies and hypoacusis, recent advances in gene discovery, the different DNA-based microarray technologies available for molecular testing, their benefits and limitations, and novel therapeutic approaches.
  Archivos de la Sociedad Espanola de Oftalmologia 01/2009; 83(12):689-702.
• Article: Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I.

  A Oshima, T Jaijo, E Aller, J M Millan, C Carney, S Usami, C Moller, W J Kimberling
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  ABSTRACT: Mutations in the human gene encoding cadherin23 (CDH23) cause Usher syndrome type 1D (USH1D) and nonsyndromic hearing loss. Individuals with Usher syndrome type I have profound congenital deafness, vestibular areflexia and usually begin to exhibit signs of RP in early adolescence. In the present study, we carried out the mutation analysis in all 69 exons of the CDH23 gene in 56 Usher type 1 probands already screened for mutations in MYO7A. A total of 18 of 56 subjects (32.1%) were observed to have one or two CDH23 variants that are presumed to be pathologic. Twenty one different pathologic genome variants were observed of which 15 were novel. Out of a total of 112 alleles, 31 (27.7%) were considered pathologic. Based on our results it is estimated that about 20% of patients with Usher syndrome type I have CDH23 mutations.
  Human Mutation 07/2008; 29(6):E37-46. · 5.69 Impact Factor
• Article: Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I

  A. Oshima, T. Jaijo, E. Aller, J.M. Millan, C. Carney, S. Usami, C. Moller, W.J. Kimberling
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  ABSTRACT: Mutations in the human gene encoding cadherin23 (CDH23) cause Usher syndrome type 1D (USH1D) and nonsyndromic hearing loss. Individuals with Usher syndrome type I have profound congenital deafness, vestibular areflexia and usually begin to exhibit signs of RP in early adolescence. In the present study, we carried out the mutation analysis in all 69 exons of the CDH23 gene in 56 Usher type 1 probands already screened for mutations in MYO7A. A total of 18 of 56 subjects (32.1%) were observed to have one or two CDH23 variants that are presumed to be pathologic. Twenty one different pathologic genome variants were observed of which 15 were novel. Out of a total of 112 alleles, 31 (27.7%) were considered pathologic. Based on our results it is estimated that about 20% of patients with Usher syndrome type I have CDH23 mutations. © 2008 Wiley-Liss, Inc.
  Human Mutation 05/2008; 29(6):E37 - E46. · 5.69 Impact Factor
• Article: MYO7A mutation screening in Usher syndrome type I patients from diverse origins.

  T Jaijo, E Aller, M Beneyto, C Najera, C Graziano, D Turchetti, M Seri, C Ayuso, M Baiget, F Moreno, C Morera, H Perez-Garrigues, J M Millan
  Journal of Medical Genetics 04/2007; 44(3):e71. · 6.36 Impact Factor
• Article: Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II.

  E Aller, T Jaijo, M Beneyto, C Nájera, S Oltra, C Ayuso, M Baiget, M Carballo, G Antiñolo, D Valverde, F Moreno, C Vilela, D Collado, H Pérez-Garrigues, A Navea, J M Millán
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  ABSTRACT: Mutations in USH2A gene have been shown to be responsible for Usher syndrome type II, an autosomal recessive disorder characterised by hearing loss and retinitis pigmentosa. USH2A was firstly described as consisting of 21 exons, but 52 novel exons at the 3' end of the gene were recently identified. In this report, a mutation analysis of the new 52 exons of USH2A gene was carried out in 32 unrelated patients in which both disease-causing mutations could not be found after the screening of the first 21 exons of the USH2A gene. On analysing the new 52 exons, fourteen novel mutations were identified in 14 out of the 32 cases studied, including 7 missense, 5 frameshift, 1 duplication and a putative splice-site mutation.
  Journal of Medical Genetics 12/2006; 43(11):e55. · 6.36 Impact Factor
• Article: Mutation profile of the MYO7A gene in Spanish patients with Usher syndrome type I.

  T Jaijo, E Aller, S Oltra, M Beneyto, C Nájera, C Ayuso, M Baiget, M Carballo, G Antiñolo, D Valverde, F Moreno, C Vilela, H Perez-Garrigues, A Navea, J M Millán
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  ABSTRACT: Usher syndrome type I is the most severe form of Usher syndrome. It is an autosomal recessive disorder characterized by profound congenital sensorineural deafness, retinitis pigmentosa, and vestibular abnormalities. Mutations in the myosin VIIA gene (MYO7A) are responsible for Usher syndrome type 1B (USH1B). This gene is thought to bear greatest responsibility for USH1 and, depending on the study, has been reported to account for between 24% and 59% of USH1 cases. In this report a mutation screening of the MYO7A gene was carried out in a series of 48 unrelated USH1 families using single strand conformation polymorphism analysis (SSCP) and direct sequencing of those fragments showed an abnormal electrophoretic pattern. Twenty-five mutations were identified in 23 out of the 48 families studied (47.9%). Twelve of these mutations were novel, including five missense mutations, three premature stop codons, three frameshift, and one putative splice-site mutation. Based on our results we can conclude there is an absence of hot spot mutations in the MYO7A gene and that this gene plays a major role in Usher syndrome.
  Human Mutation 03/2006; 27(3):290-1. · 5.69 Impact Factor
• Article: Mutation profile of the MYO7A gene in Spanish patients with Usher syndrome type I

  T. Jaijo, E. Aller, S. Oltra, M. Beneyto, C. Nájera, C. Ayuso, M. Baiget, M. Carballo, G. Antiñolo, D. Valverde, F. Moreno, C. Vilela, H. Perez-Garrigues, A. Navea, J.M. Millán
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  ABSTRACT: Usher syndrome type I is the most severe form of Usher syndrome. It is an autosomal recessive disorder characterized by profound congenital sensorineural deafness, retinitis pigmentosa, and vestibular abnormalities. Mutations in the myosin VIIA gene (MYO7A) are responsible for Usher syndrome type 1B (USH1B). This gene is thought to bear greatest responsibility for USH1 and, depending on the study, has been reported to account for between 24% and 59% of USH1 cases. In this report a mutation screening of the MYO7A gene was carried out in a series of 48 unrelated USH1 families using single strand conformation polymorphism analysis (SSCP) and direct sequencing of those fragments showed an abnormal electrophoretic pattern. Twenty-five mutations were identified in 23 out of the 48 families studied (47.9%). Twelve of these mutations were novel, including five missense mutations, three premature stop codons, three frameshift, and one putative splice-site mutation. Based on our results we can conclude there is an absence of hot spot mutations in the MYO7A gene and that this gene plays a major role in Usher syndrome. © 2006 Wiley-Liss, Inc.
  Human Mutation 02/2006; 27(3):290 - 291. · 5.69 Impact Factor
• Article: Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability.

  E Aller, T Jaijo, S Oltra, J Alió, F Galán, C Nájera, M Beneyto, J M Millán
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  ABSTRACT: Usher syndrome type III is an autosomal recessive disorder clinically characterized by the association of retinitis pigmentosa (RP), variable presence of vestibular dysfunction and progressive hearing loss, being the progression of the hearing impairment the critical parameter classically used to distinguish this form from Usher syndrome type I and Usher syndrome type II. Usher syndrome type III clinical subtype is the rarest form of Usher syndrome in Spain, accounting only for 6% of all Usher syndrome Spanish cases. The gene responsible for Usher syndrome type III is named clarin-1 and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening for mutations in clarin-1 gene among our series of Usher syndrome Spanish patients. Clarin-1 has been found to be responsible for the disease in only two families: the first one is a previously reported family homozygous for Y63X mutation and the second one, described here, is homozygous for C40G. This accounts for 1.7% of Usher syndrome Spanish families. It is noticeable that, whereas C40G family is clinically compatible with Usher syndrome type III due to the progression of the hearing loss, Y63X family could be diagnosed as Usher syndrome type I because the hearing impairment is profound and stable. Thus, we consider that the progression of hearing loss is not the definitive key parameter to distinguish Usher syndrome type III from Usher syndrome type I and Usher syndrome type II.
  Clinical Genetics 01/2005; 66(6):525-9. · 3.13 Impact Factor
• Article: [Molecular genetic study of Usher syndrome in Spain].

  T Jaijo, E Aller, M Beneyto, C Nájera, J M Millán
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  ABSTRACT: Usher syndrome (USH) associates deafness and retinitis pigmentosa (RP). It is a disease both clinically and genetically heterogeneous. It is inherited as an autosomal recessive trait and its prevalence makes it the most frequent association of hearing loss and RP. Clinically Usher syndrome is divided into type I (USH1), II (USH2) and III (USH3), according to the severity of hearing loss, age of onset of RP and the existence or not of vestibular dysfunction. There are at least 7 different localizations for USH1 and 5 genes have been identified. For USH2, 3 loci and 2 genes have been reported and USH3 is due to Clarin-1 gene. Our aim is to perform a clinical and genetic characterization of all Usher syndrome patients in Spain.
  Acta Otorrinolaringológica Española 56(7):285-9.