Vassiliki Iliadou

Prevalence of GJB2 mutations in prelingual deafness in the Greek population

OBJECTIVE Mutations in the gene encoding the gap junction protein connexin 26 (GJB2) have been shown as a major contributor to prelingual, sensorineural, nonsyndromic, recessive deafness. One specific mutation, 35delG, has accounted for the majority of the mutations detected in the GJB2 gene in Caucasian populations. The aim of our study was to determine the prevalence and spectrum of GJB2 mutations in prelingual deafness in the Greek population. METHODS In a collaboration with the major referral centers for childhood deafness in Greece, patients were examined by an extensive questionnaire to exclude syndromic forms and environmental causes of deafness and by allele-specific polymerase chain reaction (PCR) for the detection of the 35delG mutation. Patients heterozygous for the 35delG mutation were further analyzed by direct genomic sequencing of the coding region of the GJB2 gene. RESULTS The 35delG mutation was found in 42.2% of the chromosomes in 45 familial cases of prelingual, nonsyndromic deafness (18 homozygotes and 2 heterozygotes) and in 30.6% of the chromosomes in 165 sporadic cases (45 homozygotes and 11 heterozygotes). Direct genomic sequencing in heterozygous patients revealed the L90P (2 alleles), W24X (2 alleles), R184P (2 alleles), and 291insA (1 allele) mutations. CONCLUSION Mutations in the GJB2 gene are responsible for about one third of prelingual, sensorineural, nonsyndromic deafness in the Greek population, and allele-specific PCR is an easy screening method for the common 35delG mutation.

A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13-16.1

Otosclerosis is a common form of hearing impairment among white adults with a prevalence of 0.3–0.4%. It is caused by abnormal bone homeostasis of the otic capsule that compromises free motion of the stapes in the oval window. Otosclerosis is in most patients a multifactorial disease, caused by both genetic and environmental factors. In some cases, the disease is inherited as a monogenic autosomal dominant trait, sometimes with reduced penetrance. However, families large enough for genetic linkage studies are extremely rare. To date, five loci (OTSC1-5) have been reported, but none of the responsible genes have been cloned yet. An additional locus, OTSC6, has been reported to the HUGO nomenclature committee but the relevant linkage study has not been published. In this study, a genome-wide linkage study was performed in a large Greek pedigree segregating autosomal dominant otosclerosis. A seventh locus, OTSC7, was localized on chromosome 6q13–16.1 with a multipoint LOD score of 7.5 in the 13.47 cM region defined by markers D6S1036 (centromeric) and D6S300 (telomeric). Linkage analysis of this new locus in 13 smaller Belgian and Dutch families has identified one family from The Netherlands in which allele segregation suggests linkage to this region. The overlap between the critical regions of these two families is a 1.06 Mb interval between the genetic markers D6S1036 (centromeric) and D6S406 (telomeric) on chromosome 6q13.

Auditory Processing Disorders in children suspected of Learning Disabilities―A need for screening?

AIM The current study aims to assess: (a) the prevalence of auditory processing in a population of children reporting learning difficulties, (b) the correlation of APD diagnosis with age, the intelligence coefficient (IQ) and with the presence of a specific learning disability such as dyslexia and (c) to evaluate the reliability of each auditory processing test used in this study in identifying APD. METHOD We evaluated one hundred and twenty-seven consecutive children referred to the academic tertiary LD Clinic of the Psychiatric Department by means of a psychoacoustic mainly non-verbal test battery. RESULTS APD was found to be present in 43.3% and co-existing with developmental dyslexia in 25% of cases. The diagnosis of APD correlated with age in that children with APD were younger by 2 years than those without a diagnosis of APD. The diagnosis of APD did not correlate with IQ or with the diagnosis of dyslexia. INTERPRETATION High prevalence of APD in the targeted group of children suspected of Learning Disabilities sets the grounds for a possible benefit in screening for the disorder.

Bi-syllabic, Modern Greek word lists for use in word recognition tests

The development of a word recognition test for Modern Greek, which is comprised of three fifty-word lists, is described herein. The development was guided by four principles: 1) use of the shortest words possible (two syllables for Greek) 2) use of highly frequent words 3) phonetic balance and 4) appropriate balance of first and second syllable stress. The lists were recorded by one male and one female native speakers. Thirty-seven native speakers of Greek listened to all words by both speakers. Across lists, the mean correct identification score was 97.9% for the female voice (95% confidence interval 96.97 to 98.84) and 96.5% (95% confidence interval 95.31 to 97.77) for the male voice. This small difference was statistically significant (p<.01) and concentrated on words with first syllable stress. In future work, these recordings can be used in adult tests of speech perception and can be modified for tests of central auditory processing. Sumario Se describe el desarrollo de una prueba de discriminación en griego moderno a partir de tres listas de cincuenta palabras. Este desarrollo se basó en tres principios: 1. Uso de las palabras más cortas posibles en Griego (bisilábicos); 2. Uso de palabras altamente frecuentes; 3. Balance fonético 4. Balance apropiado entre el acento inicial y final. Las palabras fueron grabadas por un hombre y una mujer nativos del idioma. 37 personas nativos del idioma griego escucharon todas las palabras con ambas voces. En todas las listas, el porcentaje de identificación correcto fue del 97% para la voz femenina (Intervalo de confianza de 95% de 96.97 a 98.84) y 96.5% (intervalo de confianza del 95%, de 95.31 a 97.7%) para la voz masculina. Esta pequeña diferencia fue estadísticamente significativa (p<.01) y se concentró en las palabras con acento en la primera sílaba. Estas grabaciones pueden ser utilizadas en futuros trabajos para pruebas de percepción del lenguaje en adultos y pueden ser modificadas para pruebas de procesamiento central auditivo.

Hemispheric laterality assessment with dichotic digits testing in dyslexia and auditory processing disorder

Abstract One of the widely used tests to evaluate functional asymmetry of cerebral hemispheres is the dichotic listening test with the usually prevailing right ear advantage. The current study aims at assessing hemispheric laterality in an adult sample of individuals with dyslexia, with auditory processing disorder (APD), and adults experiencing comorbidity of the two mentioned disorders against a control group with normal hearing and absence of learning disabilities. Results exhibit a right hemispheric dominance for the control and APD group, a left hemispheric dominance for the group diagnosed with both dyslexia and APD, and absence of dominance for the dyslexia group. Assessment of laterality was repeatable and produced stable results, indicating a true deficit. A component of auditory processing, specifically the auditory performance in competing acoustic signals, seems to be deficient in all three groups, and laterality of hemispheric functions influenced at least for auditory-language stimuli in the two of the three groups, one being adults with dyslexia and the other being adults with comorbidity of dyslexia and APD. Sumario Una de las pruebas más ampliamente utilizadas para evaluar la asimetría funcional de los hemisferios cerebrales es la prueba de escucha dicótica, generalmente con la resultante ventaja del oído derecho. El presente estudio tiene como objetivo evaluar la lateralidad hemisférica en una muestra de adultos con dislexia, con desórdenes del procesamiento auditivo (APD) y adultos con ambos problemas vs un grupo control de normoyentes sin alteraciones del aprendizaje. Los resultados muestran una dominancia del hemisferio derecho para el grupo control y el grupo con APD y una dominancia del hemisferio izquierdo para el grupo diagnosticado con ambas condiciones, y ninguna dominancia del grupo de dislexia. La evaluación de la lateralidad fue repetible y produjo resultados estables, indicando un déficit verdadero. Un componente del procesamiento auditivo, específicamente el desempeño auditivo bajo señales acústicas competitivas, parece ser deficiente en los tres grupos y las funciones de lateralidad hemisférica se vieron influidas al menos por los estímulos auditivos lingüísticos en dos de los tres grupos; el de adultos con dislexia y el de adultos con ambas condiciones, dislexia y APD.

Strong linkage disequilibrium for the frequent GJB2 35delG mutation in the Greek population.

Approximately one in 1,000 children is affected by severe or profound hearing loss at birth or during early childhood (prelingual deafness). Up to 40% of congenital, autosomal recessive, severe to profound hearing impairment cases result from mutations in a single gene, GJB2, that encodes the connexin 26 protein. One specific mutation in this gene, 35delG, accounts for the majority of GJB2 mutations detected in Caucasian populations. Some previous studies have assumed that the high frequency of the 35delG mutation reflects the presence of a mutational hot spot, while other studies support the theory of a common founder. Greece is among the countries with the highest carrier frequency of the 35delG mutation (3.5%), and a recent study raised the hypothesis of the origin of this mutation in ancient Greece. We genotyped 60 Greek deafness patients homozygous for the 35delG mutation for six single nucleotide polymorphisms (SNPs) and two microsatellite markers inside or flanking the GJB2 gene. The allele distribution in the patients was compared to 60 Greek normal hearing controls. A strong linkage disequilibrium was found between the 35delG mutation and markers inside or flanking the GJB2 gene. Furthermore, we found a common haplotype with a previous study, suggesting a common founder for the 35delG mutation.

Psychophysiology and psychoacoustics of music: Perception of complex sound in normal subjects and psychiatric patients

Perception of complex sound is a process carried out in everyday life situations and contributes in the way one perceives reality. Attempting to explain sound perception and how it affects human beings is complicated. Physics of simple sound can be described as a function of frequency, amplitude and phase. Psychology of sound, also termed psychoacoustics, has its own distinct elements of pitch, intensity and tibre. An interconnection exists between physics and psychology of hearing.Music being a complex sound contributes to communication and conveys information with semantic and emotional elements. These elements indicate the involvement of the central nervous system through processes of integration and interpretation together with peripheral auditory processing.Effects of sound and music in human psychology and physiology are complicated. Psychological influences of listening to different types of music are based on the different characteristics of basic musical sounds. Attempting to explain music perception can be simpler if music is broken down to its basic auditory signals. Perception of auditory signals is analyzed by the science of psychoacoustics. Differences in complex sound perception have been found between normal subjects and psychiatric patients and between different types of psychopathologies.

Audiological profile of the prevalent genetic form of childhood sensorineural hearing loss due to GJB2 mutations in northern Greece

The present study describes the audiological profile of genetic hearing loss resulting from GJB2 mutations in northern Greece, as this represents the most frequent single cause of childhood sensorineural hearing loss. The 35delG mutation in homozygosity was detected in 27 of 107 patients (25.2%). The audiological profile is that of a profound or severe sensorineural hearing loss, with a sloping or flat configuration of the audiogram, mostly symmetrical, non-progressive and affecting more the higher frequencies. This profile underlines the importance of early identification and genetic family counseling leading to the future possibility of prevention of deafness.

Prelingual Nonsyndromic Hearing Loss in Greece

Mutations in the gene encoding the gap-junction protein connexin 26 (GJB2) on chromosome 13q11 have been shown as a major contributor to prelingual, sensorineural, nonsyndromic deafness. One specific mutation, 35delG, has accounted for the majority of the mutations detected in the GJB2 gene in Caucasian populations and is one of the most frequent disease mutations identified so far with highest carrier frequency of 3,5% in the Greek population. In a collaboration with the major referral centers for childhood deafness in Greece, patients were examined by an extensive questionnaire to exclude syndromic forms and environmental causes of deafness and by allele-specific PCR for the detection of the 35delG mutation. The 35delG mutation was found in 32.1% of the alleles in 173 unrelated cases of prelingual deafness: 50 homozygotes and 11 heterozygotes. Individuals heterozygous for the 35delG mutation were further analyzed by direct genomic sequencing of the coding region of the GJB2 gene, which revealed R184P and 486insT mutations in single alleles. We conclude that the 35delG GJB2 mutation is responsible for one third of prelingual, sensorineural deafness in Greece, which is higher than the usually quoted 20% for Caucasian populations.

Comparative Laterality in (central) auditory processing disorders and dyslexia

Results Percentages of correct identification of digits were calculated separately for each ear and the scores were organized and analyzed according to the four subject groups. Group 1: normal children, Group 2: children diagnosed with dyslexia, Group 3: children diagnosed with (C)APD and Group 4: children diagnosed with both dyslexia and (C)APD. Mean scores for the right ear were 90.25, 86.88, 76.50 and 70.83 for groups 1,2,3 and 4 respectively and for the left ear 88, 84.58, 70.83, 70.83.