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Biomedical subjects

M Mazzoli

Publications and source records attributed to M Mazzoli.

At least 19 recordsLinked to original sources
PubMed2003

Mapping of a new autosomal dominant non-syndromic hearing loss locus (DFNA43) to chromosome 2p12.

Hearing impairment (HI) is the most frequent sensory defect with wide genetic heterogeneity. Approximately 80% of genetic hearing loss is non-syndromic and 15-25% of exhibit autosomal dominant inheritance. We analysed an Italian three generation family in which non-syndromic hearing impairment is transmitted as an autosomal dominant trait. Onset of HI in all affected subjects occurred in the second decade of life, with subsequent gradual progression from moderate to profound loss. HI was bilateral and symmetrical, involving all frequencies. After exclusion of the known DFNA loci with markers from the Hereditary Hearing Loss Homepage (URL: http://dnalab-www.uia.ac.be/dnalab/hhh), a genome wide scan was carried out using 358 highly informative microsatellite markers. Significant linkage (Zmax=4.21, theta=0) was obtained with chromosome 2p12 markers. The results were confirmed by multipoint analysis (Zmax=4.51), using the location score method. Haplotype analysis defined a 9.6 cM disease gene interval on chromosome 2 without overlap with the other identified loci. Fine mapping and identification of candidate genes are in progress.

Chromosome Mapping↗
PubMed2002

Exploring the clinical and epidemiological complexity of GJB2-linked deafness.

GJB2 mutation analysis was performed in 179 unrelated subjects with sporadic or familial hearing loss (HL). Among 57 families, 18 showed a vertical transmission of HL, the disease being present in two or three generations. Besides 155 nonsyndromic cases, 24 patients presenting with extra-auditory clinical signs were included in the molecular study. GJB2 mutation analysis was also performed in 19 subjects with an anamnestic history of perinatal risks factors for acquired HL. The 35delG mutation accounted for 22.1% of analyzed chromosomes in sporadic cases and 39.4% in familial cases; 35delG prevalence reached 41% in autosomal recessive and 44.4% in pseudodominant pedigrees. Two novel GJB2 mutations were identified in compound heterozygosity with 35delG allele (D159V, 284ins/dup[CACGT]). Two 35delG homozygous subjects were identified among HL cases classified as environmental in origin. Four patients 35delG heterozygous (35delG/V95M, 35delG/L90P, 35delG/167delT, and 35delG/?) and two homozygous presented with extra-auditory clinical signs involving different organs (skin, vascular system, hemopoietic lineages, and thyroid). In a high proportion of 35delG heterozygous HL patients (52%), no second GJB2 mutation was detected. The reported data highlight the complexity of the genetic epidemiology of GJB2-linked deafness, further enlarging the spectrum of situations in which GJB2 mutation analysis should be performed. The presence of extra-auditory signs in a significant portion of GJB2-mutated patients suggests the possibility that GJB2 loss of function could contribute to clinical phenotypes presenting in association with deafness. This hypothesis deserves further investigation. The failure to identify a presumed partnering GJB2 mutation in a high proportion of deaf patients remains a challenging problem to be clarified.

Amino Acid Sequence↗
PubMed2001

Mapping of a new autosomal dominant nonsyndromic hearing loss locus (DFNA30) to chromosome 15q25-26.

Hearing impairment is the most common inherited human sensory defect. Nonsyndromic Hearing Impairment (NSHI) is the most genetically heterogeneous trait known. Over 70 loci have been mapped and a total of 19 genes have been identified. We report here a novel locus (DFNA 30) for autosomal dominant NSHI that we mapped to chromosome 15q25-26 in an Italian four-generation family. The haplotype analysis has identified a critical interval of 18 cM between markers D15S151 and D15S130. This region does not overlap with DFNB16 locus but partially coincides with the otosclerosis (OTS) locus. Localisation of the locus DFNA30 is a first step towards the identification of the gene.

Chromosome Mapping↗
PubMed1999

Achievements of the European Working Group on Genetics of Hearing Impairment.

Three years ago an European Working Group for the study of genetics of hearing impairment was founded with the aim to standardise terminology and protocols in order to collect families with genetic hearing impairments for a European-based epidemiological, clinical and genetic analysis. Hereditary hearing impairments include a large variety of genetic causes. The occurrence of the different forms is rare, but the overall genetic aetiology is thought to account for up to 50% of newborns' hearing impairment as well as several late onset, progressive cases. In the later years, several locations associated with non-syndromal hearing impairments and different mutations for the syndromic diseases have been identified. Five subgroups have been formed: Definitions and protocols, Epidemiology, Vestibular involvement, Otological and cranial malformations, Molecular biology. Meetings were organised for discussion and establishment of common ground work. Application of the agreed documents was performed to verify protocols. Final agreements were circulated by Infoletter (1-5). Informatic working tools on the Internet have been designed. Standardised definitions, audiological and vestibular protocols have been defined. Pilot studies using experimental protocols to identify informative carriers or to help clinical differentiation between non-syndromic forms have also been performed. Two web sites related to the work have been created. A description of phenotypes of locations identified has been defined. Joining forces to standardise definitions and protocols and collaboration between clinicians and geneticists has contributed considerably to progress in this field.

Europe↗
PubMed1997

An introduction to the genetics of normal and defective hearing.

The recent rapid development of molecular biology techniques applied to the genetics of normal and defective hearing shed a new light on old questions regarding hearing and deafness. Genes are DNA sequences that determine characteristics, normally by specifying the sequence of aminoacids in a protein. The majority of genes is located in the chromosomes (human chromosomes have perhaps 80,000 pairs of genes). In addition there are 37 mithochondrial genes which are inherited only from the mother. One method used to identify candidate genes based on their function or pattern of tissue expression involves the construction of cDNA libraries from the target organ or tissue, in this case from the cochlea. The construction and characterization of cochlear cDNA libraries from humans and other species provide an important resource for rapid identification of cochlear genes involved in normal hearing and hearing disorders. Studies of the molecular genetics of the inner ear are hampered by the relative inaccessibility of the cochlea, by the limited number of cochlear and vestibular cells, and by our inability to maintain many of these cell types in long-term cultures. Several rodent inner-ear cDNA libraries and a human foetal cochlear cDNA library have already been constructed. Human and rodent cochlea-subtracted cDNA libraries are very useful for identifying genes controlling the development and maintenance of hearing. cDNA libraries constructed at different stages of development, and subtracted from each other, could be instrumental in identifying genes important at each stage of cochlear development. In addition, these libraries have the potential of fostering the identification of other proteins unique to the cochlea and will contribute to the identification, characterization, and functional analysis of these cochlea-specific proteins. Another important application of cDNA libraries is in identifying hearing-loss genes. Once the candidate gene for a given type of hearing loss is cloned and decoded, the structure of its protein product can be determined. This will provide insights into the biochemical function of the gene product in normal cochlear tissue, and will show why the genetic mutation results in hearing loss, that is, the recent identification of the myosin VIIa gene in Usher type IB. In addition, through the use of homologous recombination and transgenic technology, in vivo mouse models of inner-ear genetic disorders can be created. To date, 350 different genetic conditions associated with hearing impairment have been described, and during the past five years several of the genes involved in these form have already been mapped and identified.

Animals↗
PubMed1993

Efficacy and tolerability of brodimoprim in bacterial otitis media in children. Controlled study versus cefaclor.

78 pediatric patients affected by acute otitis media were selected and randomized into two balanced groups of treatment: brodimoprim, at the dosage of 200 mg once-a-day on the first day and of 100 mg once-a-day on the following days, and cefaclor at a dosage of 40 mg/Kg/day in three doses. Brodimoprim resulted more efficacious in the reduction of symptoms, especially hypoacusis and tinnitus (p < 0.05 between treatments); tympanometry showed a higher number of normalizations in the brodimoprim group, without significant differences between treatments. Both drugs resulted active against most of isolated bacterial strains. Side effects were reported in 4 patients treated with brodimoprim and in 6 patients in the control group.

Acute Disease↗
PubMed1992

A follow-up and family study of DSM-III-R schizophreniform disorder with good prognostic features.

A follow-up and family study was carried out of 16 first episode, DSM-III-R schizophreniform disorder patients with good prognostic features. Mean length of follow-up was 52.3 months. It was found that 62.5% had affective episodes, 31.2% had schizophreniform episodes. No case of schizophrenia was observed. Outcome was good. Morbid risk for affective disorder among first degree relatives was 25%, morbid risk for schizophrenia was 0%. These findings suggest a link between DSM-III-R schizophreniform disorder with good prognostic features and affective disorder, and no relationship with schizophrenia.

Adolescent↗