Publications (71)380.37 Total impact
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Article: Stickler and branchio-oto-renal syndromes in a patient with mutations in EYA1 and COL2A1 genes.
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ABSTRACT: Branchio-oto-renal (BOR) and Stickler (STL) syndromes are disorders that include hearing loss among their clinical features. STL syndrome type I (STL1) is a combination of ophthalmic, orofacial, articular, and auditory manifestations, caused by mutations in the COL2A1. BOR syndrome is an autosomal dominant trait encompassing branchial, otic and renal anomalies because of mutations in EYA1, SIX1 and SIX5. In this study, we have clinically and genetically diagnosed a proband that displayed STL1 and BOR syndromes. This patient and his younger brother exhibited hearing loss and cleft palate. Both siblings and their mother also showed myopia, congenital non-progressive vitreous anomaly and a flat face. Taken together, these clinical features are consistent with the diagnosis of a familial case of STL. Sequence analysis revealed in the three patients a novel COL2A1 mutation (c.1468_1475delinsT) that accounted for a STL1 phenotype. The proband also displayed pre-auricular pits, branchial fistulae and renal agenesis that define BOR syndrome. Interestingly, this patient carries an EYA1 mutation, p.R328X, which was not present in the two other patients or in his healthy father, supporting that the mutation arose de novo. In conclusion, this report highlights the importance of molecular testing and detailed clinical evaluation for the diagnosis of syndromes with overlapping phenotypic features.Clinical Genetics 04/2008; 73(3):262-7. · 3.13 Impact Factor -
Article: Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C->T mutation in the mitochondrial 12S rRNA gene.
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ABSTRACT: Mutations in the 12S rRNA gene of the mitochondrial genome are responsible for maternally inherited non-syndromic hearing loss (NSHL), and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. Among these mutations, 1555A-->G is the most prevalent in all populations tested so far. Recently, the 1494C-->T mutation was reported in two large Chinese pedigrees with maternally inherited NSHL. In this study, sequencing of the 12S rRNA gene in a Spanish family with maternally inherited NSHL showed the presence of the 1494C-->T mutation. An additional screening of 1339 unrelated Spanish patients with NSHL allowed the authors to find two other families with the mutation. Audiological data were obtained from 17 confirmed 1494C-->T carriers, which showed that the hearing loss was sensorineural, bilateral and symmetrical, with a remarkable variability in age of onset and severity. Three carriers were asymptomatic. Three affected carriers had a history of treatment with aminoglycoside antibiotics. The mitochondrial genome of one affected person from each of these three families was entirely sequenced, and it was established that they belong to different mitochondrial haplogroups (H, U5b, U6a). The study results further support the pathogenic role of 1494C-->T on hearing, and show that this mutation can be found in different Caucasian mitochondrial DNA backgrounds.Journal of Medical Genetics 12/2006; 43(11):e54. · 6.36 Impact Factor -
Article: [Prevalence of the 35delG mutation in the GJB2 gene, del (GJB6-D13S1830) in the GJB6 gene, Q829X in the OTOF gene and A1555G in the mitochondrial 12S rRNA gene in subjects with non-syndromic sensorineural hearing impairment of congenital/childhood onset].
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ABSTRACT: The most frequent mutations responsible for non-syndromic hearing impairment in the Spanish population are the 35delG mutation in the connexin 26 gene (GJB2), the del(GJB6-D13S1830) deletion in the connexin 30 gene (GJB6), the Q829X mutation in the otoferlin gene (OTOF), and the A1555G mutation in the 12S rRNA gene of the mitochondrial genome. Screening for these mutations was performed on 38 patients from Cantabria with non-syndromic sensorineural hearing impairment of congenital/childhood onset. The A1555G mutation was detected in homoplasmy in 9 patients (23.7%). Three individuals were heterozygous for the 35delG mutation (7.9%). The heterozygous del(GJB6-D13S1830) deletion was present in one case (2.6%). One subject was homozygous for the Q829X mutation (2.6%). These four mutations are present in 36.8% of all cases of non-syndromic hearing impairment in our population.Acta Otorrinolaringológica Española 01/2006; 56(10):463-8. -
Article: A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment.
Journal of Medical Genetics 08/2005; 42(7):588-94. · 6.36 Impact Factor -
Article: Pendred's syndrome and non-syndromic DFNB4 deafness associated with the homozygous T410M mutation in the SLC26A4 gene in siblings.
Clinical Genetics 06/2005; 67(5):438-40. · 3.13 Impact Factor -
Article: [Prevalence of the A1555G mutation in the mitochondrial DNA in patients with cochlear or vestibular damage due to aminoglycoside-induced ototoxicity].
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ABSTRACT: To determine the frequency of the A1555G mutation in the mitochondrial genome among Spanish patients with aminoglycoside-induced ototoxicity. We screened 25 unrelated cases, totalling 39 individuals with cochlear or vestibular damage due to aminoglycoside-induced ototoxicity. This group was made up of 18 subjects from 4 unrelated families with a history of aminoglycoside ototoxicity in more than one relative, 8 subjects from 8 families that also had other relatives with hearing loss in absence of aminoglycoside exposure, and 13 sporadic cases. Among the 13 sporadic cases, there were 3 patients with vestibular involvement. Detection of the A1555G mutation was seen by mean of techniques for molecular diagnosis. The A1555G mutation was identified in all of the individuals from 4 families with aminoglycoside-induced cochlear damage and in 6 of 8 individuals with familial hearing loss. None of the sporadic cases carried the mutation. A high proportion of patients with cochlear damage due to aminoglycoside ototoxicity and having a familial history of hearing loss, related or not to aminoglycoside exposure, harbor the A1555G mutation.Acta Otorrinolaringológica Española 06/2004; 55(5):212-7. -
Article: A novel locus for autosomal dominant nonsyndromic hearing loss, DFNA50, maps to chromosome 7q32 between the DFNB17 and DFNB13 deafness loci.
Journal of Medical Genetics 03/2004; 41(2):e14. · 6.36 Impact Factor -
Article: A genotype-phenotype correlation for GJB2 (connexin 26) deafness.
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ABSTRACT: Mutations in GJB2 are the most common cause of non-syndromic autosomal recessive hearing impairment, ranging from mild to profound. Mutation analysis of this gene is widely available as a genetic diagnostic test. To assess a possible genotype-phenotype correlation for GJB2. Retrospective analysis of audiometric data from people with hearing impairment, segregating two GJB2 mutations. Two hundred and seventy seven unrelated patients with hearing impairment who were seen at the ENT departments of local and university hospitals from Italy, Belgium, Spain, and the United States, and who harboured bi-allelic GJB2 mutations. We found that 35delG homozygotes have significantly more hearing impairment, compared with 35delG/non-35delG compound heterozygotes. People with two non-35delG mutations have even less hearing impairment. We observed a similar gradient of hearing impairment when we categorised mutations as inactivating (that is, stop mutations or frame shifts) or non-inactivating (that is, missense mutations). We demonstrated that certain mutation combinations (including the combination of 35delG with the missense mutations L90P, V37I, or the splice-site mutation IVS1+1G>A, and the V37I/V37I genotype) are associated with significantly less hearing impairment compared with 35delG homozygous genotypes. This study is the first large systematic analysis indicating that the GJB2 genotype has a major impact on the degree of hearing impairment, and identifying mild genotypes. Furthermore, this study shows that it will be possible to refine this correlation and extend it to additional genotypes. These data will be useful in evaluating habilitation options for people with GJB2 related deafness.Journal of Medical Genetics 03/2004; 41(3):147-54. · 6.36 Impact Factor -
Article: DFNA49, a novel locus for autosomal dominant non-syndromic hearing loss, maps proximal to DFNA7/DFNM1 region on chromosome 1q21-q23.
Journal of Medical Genetics 12/2003; 40(11):832-6. · 6.36 Impact Factor -
Article: Uniparental disomy of chromosome 13q causing homozygosity for the 35delG mutation in the gene encoding connexin26 (GJB2) results in prelingual hearing impairment in two unrelated Spanish patients.
Journal of Medical Genetics 09/2003; 40(8):636-9. · 6.36 Impact Factor -
Article: Heteroplasmy for the 1555A>G mutation in the mitochondrial 12S rRNA gene in six Spanish families with non-syndromic hearing loss.
Journal of Medical Genetics 09/2003; 40(8):632-6. · 6.36 Impact Factor -
Article: Maternally inherited non-syndromic hearing impairment in a Spanish family with the 7510T>C mutation in the mitochondrial tRNA(Ser(UCN)) gene.
Journal of Medical Genetics 01/2003; 39(12):e82. · 6.36 Impact Factor -
Article: [Incidence of A1555G mutations in the mitochondrial DNA and 35delG in the GJB2 gene (connexin-26) in families with late onset non-syndromic sensorineural hearing loss from Cantabria].
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ABSTRACT: Sensorineural deafness is a very common disorder in humans, which affects approximately 10% of the population. Genetic causes are suggested to be responsible for more than half of the cases. The A1555G mutation in the mitochondrial 12S rRNA gene and the 35delG mutation in the GJB2 gene are the most common mutations for sensorineural deafness in the Spanish population. A genetic study was carried out in order to determine the frequency of the mutations A1555G in the mitochondrial DNA and 35delG in the connexin-26 gene in 21 patients from 21 non-consanguineous unrelated families affected by late-onset bilateral non-syndromic sensorineural hearing loss from Cantabria. The A1555G mutation was found in 6 patients. Five of these 6 patients had been treated with aminoglycosides. In all of them the auditory impairment affected mainly the high frequencies. The 35delG mutation was not found in any of the patients. The A1555G mutation in the mitochondrial DNA has been found to be the most common amongst the Cantabrian population. The A1555G mutation should be suspected in those members of families affected by sensorineural hearing impairment with a maternal inheritance pattern and ototoxicity from treatment with aminoglycoside antibiotics. The 35delG mutation in the GJB2 gene does not seem to be a major cause of deafness in families with late-onset non-syndromic sensorineural hearing loss in our area.Acta Otorrinolaringológica Española 11/2002; 53(8):563-71. -
Article: Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss.
Journal of Medical Genetics 08/2002; 39(7):502-6. · 6.36 Impact Factor -
Article: Secretion of the Escherichia coli K-12 SheA hemolysin is independent of its cytolytic activity.
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ABSTRACT: The Escherichia coli K-12 sheA gene encodes a pore-forming hemolysin that is secreted to the medium by a hitherto unidentified mechanism. To study SheA secretion, we constructed fusions between SheA and the mature form of the periplasmic enzyme beta-lactamase, and performed site-directed mutagenesis on these constructs. The SheA-Bla and Bla-SheA hybrid proteins displayed hemolytic activity and were efficiently exported to the extracellular medium. Our results with mutant hybrid proteins show that secretion of SheA is independent of its cytolytic activity, that secretion is paralleled by a transient leakage of periplasmic contents to the extracellular medium, and that deletion of the 11 C-terminal residues of SheA has no effect on its secretion and cytolytic activity.FEMS Microbiology Letters 12/2001; 204(2):281-5. · 2.04 Impact Factor -
Article: A cysteine substitution in the zona pellucida domain of alpha-tectorin results in autosomal dominant, postlingual, progressive, mid frequency hearing loss in a Spanish family.
Journal of Medical Genetics 06/2001; 38(5):E13. · 6.36 Impact Factor -
Article: Construction and characterization of mutations at codon 751 of the Escherichia coli gyrB gene that confer resistance to the antimicrobial peptide microcin B17 and alter the activity of DNA gyrase.
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ABSTRACT: Microcin B17 is a peptide antibiotic that inhibits DNA replication in Escherichia coli by targeting DNA gyrase. Previously, two independently isolated microcin B17-resistant mutants were shown to harbor the same gyrB point mutation that results in the replacement of tryptophan 751 by arginine in the GyrB polypeptide. We used site-directed mutagenesis to construct mutants in which tryptophan 751 was deleted or replaced by other amino acids. These mutants exhibit altered DNA gyrase activity and different levels of resistance to microcin B17.Journal of Bacteriology 04/2001; 183(6):2137-40. · 3.83 Impact Factor -
Article: Sensorineural hearing loss and Mondini dysplasia caused by a deletion at locus DFN3.
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ABSTRACT: To study a family with inner ear malformations and sensorineural hearing loss. Clinical, radiological, and genetic study of the members of a family with different degrees of sensorineural hearing loss. The males in the family manifested profound congenital hearing loss with severe inner ear malformations, while the only affected female had progressive hearing loss that had begun during puberty. Computed tomography showed inner ear malformations in both males, with enlarged internal auditory meatus and Mondini dysplasia. Genetic analysis disclosed a microdeletion at the locus DFN3 on chromosome X. A familial Mondini dysplasia is associated to a microdeletion at the deafness locus DFN3.Archives of Otolaryngology - Head and Neck Surgery 10/2000; 126(9):1065-9. · 1.63 Impact Factor -
Article: Characterization of the genes encoding the SheA haemolysin in Escherichia coli O157:H7 and Shigella flexneri 2a.
Research in Microbiology 05/2000; 151(3):229-30. · 2.76 Impact Factor -
Article: X-linked non-syndromic sensorineural deafness: the DFN6 locus.
Advances in oto-rhino-laryngology 02/2000; 56:200-2.
Top co-authors
Top Journals
Institutions
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2004–2006
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Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain
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1988–2006
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Hospital Universitario Ramón y Cajal
- Unidad de Genética Molecular
Madrid, Madrid, Spain
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1997
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Centro De Biología Molecular Severo Ochoa
Madrid, Madrid, Spain
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1987–1992
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Harvard University
- Department of Microbiology and Molecular Genetics
Boston, MA, USA
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