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Biomedical subjects

Natalie Loundon

Publications and source records attributed to Natalie Loundon.

6 recordsLinked to original sources
PubMed2005

GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients.

OBJECTIVES: To analyze the clinical features of hearing impairment and to search for correlations with the genotype in patients with DFNB1. DESIGN: Case series. SETTING: Collaborative study in referral centers, institutional practice. Patients A total of 256 hearing-impaired patients selected on the basis of the presence of biallelic mutations in GJB2 or the association of 1 GJB2 mutation with the GJB6 deletion (GJB6-D13S1830)del. MAIN OUTCOME MEASURES: The prevalence of GJB2 mutations and the GJB6 deletion and audiometric phenotypes related to the most frequent genotypes. RESULTS: Twenty-nine different GJB2 mutations were identified. Allelic frequency of 35delG was 69%, and the other common mutations, 313del14, E47X, Q57X, and L90P, accounted for 2.6% to 2.9% of the variants. Concerning GJB6, (GJB6-D13S1830)del accounted for 5% of all mutated alleles and was observed in 25 of 93 compound heterozygous patients. Three novel GJB2 mutations, 355del9, V95M, and 573delCA, were identified. Hearing impairment was frequently less severe in compound heterozygotes 35delG/L90P and 35delG/N206S than in 35delG homozygotes. Moderate or mild hearing impairment was more frequent in patients with 1 or 2 noninactivating mutations than in patients with 2 inactivating mutations. Of 93 patients, hearing loss was stable in 73, progressive in 21, and fluctuant in 2. Progressive hearing loss was more frequent in patients with 1 or 2 noninactivating mutations than in those with 2 inactivating mutations. In 49 families, hearing loss was compared between siblings with similar genotypes, and variability in terms of severity was found in 18 families (37%). CONCLUSION: Genotype may affect deafness severity, but environmental and other genetic factors may also modulate the severity and evolution of GJB2-GJB6 deafness.

Chromosome Deletion↗
PubMed2004

Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene.

Mutations in GJB2 are the most common cause of congenital nonsyndromic hearing loss. The controversial allele variant M34T has been hypothesized to cause autosomal dominant or recessive nonsyndromic hearing impairment and some in vitro data has been consistent with this hypothesis. In this report, we present the clinical and genotypic study of 11 families (seven familial forms of nonsyndromic sensorineural hearing loss (NSSNHL) and four sporadic cases) in which the M34T GJB2 variant has been identified. The M34T mutation did not segregate with the deafness in six of the seven familial forms of NSSNH. Eight persons with normal audiogram presented a heterozygous M34T variation and five normal hearing individuals were composite heterozygous for M34T and another GJB2 mutation. Four normal hearing individuals with a documented audiogram were M34T/35delG and one was M34T/(GJB6-D13S1830)del. Screening a French control population of 116 subjects we have found an M34T allele frequency of 1.72%. This percentage was not significatively different from the prevalence of the M34T allele in the deaf population, which was 2.12%. All these data suggest that the M34T variant is not clinically significant in human and is a frequent polymorphism in France.

Connexin 26↗
PubMed2003

Usher syndrome and cochlear implantation.

OBJECTIVE: To evaluate the symptoms leading to diagnosis and the quality of rehabilitation after cochlear implantation in Usher syndrome. STUDY DESIGN: Retrospective cohort study. SETTING: ENT department of a tertiary referral hospital. PATIENTS: Among 210 patients given an implantation in the Ear, Nose, and Throat department, 185 were congenitally deaf and 13 had Usher syndrome (7.0%). Five had a family history of Usher, and eight were sporadic cases. Eleven cases were Usher type I, one was Usher type III, and one was not classified. The age at implantation ranged from 18 months to 44 years (mean, 6 years 1 month). The mean follow-up was 52 months (range, 9 months to 9 years). MAIN OUTCOME MEASURES: All patients had audiophonological and clinical examination, computed tomography scan of the temporal bones, ophthalmologic examination with fundoscopy, and an electroretinogram. Cerebral magnetic resonance imaging and vestibular examination were performed in 9 of 13 and 10 of 13 cases, respectively. Logopedic outcome measured preimplant and postimplant closed- and open-set word recognition and oral expression at follow-up. RESULTS: The most frequent initial sign of Usher syndrome was delayed walking, with a mean age of 20 months. Among the 172 other congenitally deaf children with implants, when deafness was not associated with other neurologic disorders, the mean age at walking was 14 months (p < 0.001). The fundoscopy was always abnormal after the age of 5 years, and the electroretinogram was abnormal in all cases. Vestibular function was abnormal in all but one case (nonclassified). The computed tomography scan and the magnetic resonance imaging were always normal. Logopedic results with cochlear implants showed good perception skills in all but one case. The best perceptive results were obtained in children implanted before the age of 9 years. Oral language had significantly progressed in 9 of 13 at follow-up. There was no relation between the visual acuity and the logopedic results. CONCLUSION: The earliest clinical sign associated with deafness evoking Usher syndrome is late walking. The electroretinogram is the only reliable examination to enable the diagnosis. When severe profound deafness is associated with late walking, the electroretinogram should be systematically proposed. Logopedic results are linked to precocity of implantation, and early Usher's diagnosis contributes to optimize speech therapy.

Age Factors↗