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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 73 records · Page 4Linked to original sources
PubMed1999

Prevention by 5-HT1A receptor agonists of restraint stress- and yohimbine-induced release of cholecystokinin in the frontal cortex of the freely moving rat.

In line with the idea that cholecystokinin (CCK) is involved in anxiety-related behaviours, previous investigations showed that stressful conditions and an 'anxiogenic' drug, yohimbine, increased the cortical release of CCK like-material (CCKLM) in awake rats, and that this effect could be prevented by diazepam. Here, we investigated whether other anxiolytic drugs such as 5-HT1A receptor agonists could also affect cortical CCKLM release. Indeed, neither buspirone (1 mg/kg i.p.), alnespirone (1 mg/kg i.p.) nor lesopitron (3 mg/kg i.p.) affected, on their own, CCKLM release. However, pretreatment with the latter drugs completely abolished the stimulatory effect of restraint stress on the peptide outflow. As expected of the involvement of 5-HT1A receptors, tertatolol (10 mg/kg i.p) markedly reduced the inhibitory effect of buspirone on restraint stress-evoked CCKLM overflow. On the other hand, pretreatment with buspirone, alnespirone or lesopitron also inhibited the stimulatory effect of yohimbine (5 mg/kg i.p.) on cortical CCKLM outflow. These data support the idea that the anxiolytic action of 5-HT1A receptor agonists could be mediated, at least partly, through their inhibitory influence on cortical CCK-ergic systems.

Adrenergic alpha-Antagonists↗
PubMed1999

The neuropeptide FF analogue, 1DME, enhances in vivo met-enkephalin release from the rat spinal cord.

Behavioural studies have suggested that endogenous opioids mediate the antinociceptive action of neuropeptide FF (FLFQPQRF-NH2) at the spinal level in the rat. This hypothesis was directly assessed by investigating the effects of a NPFF analogue, 1DMe ([D-Tyr1,(NMe)Phe3]NPFF), on the spinal outflow of met-enkephalin-like material (MELM) in halothane-anaesthetised rats. Intrathecal infusion (0.1 ml/min) of 1DMe (0.1 microM-0.1 mM, for 45 min) produced a concentration-dependent increase in spinal MELM outflow which persisted for at least 90 min at the highest concentration tested. Intrathecal coadministration of the micro-opioid receptor antagonist CTOP (1 microM) did not significantly affect the spinal MELM overflow due to 0.1 mM 1DMe. In contrast, both naltrindole and nor-binaltorphimine, at concentrations (10 microM) that allow the selective blockade of alpha- and kappa-opioid receptors, respectively, significantly reduced the stimulatory effect of 1DMe on spinal MELM outflow. These data provide the first direct demonstration that met-enkephalin (among other opioid peptides) can mediate the antinociceptive action of NPFF at the spinal level in rats. In addition, they suggest that reciprocal excitatory interactions between opioids and opioid-modulatory factors (such as NPFF) participate in the physiological control of nociception.

Analgesics↗
PubMed1999

Effects of chronic antidepressants in an operant conflict procedure of anxiety in the rat.

The effects of chronic antidepressants were investigated in an animal procedure for the study of anxiety and anxiolytics, the conditioned suppression of operant behavior in rats. In daily 18-min sessions, three periods of nonpunished lever pressing for food alternated with two 4-min periods signaled by a light-on conditioned stimulus during which 50% of the responses were randomly punished by electric foot shocks. Antidepressants were administered once daily for 7-8 weeks to trained, food-restricted rats. Desipramine (dose regimen increase from 4 to 16 mg/kg/day) induced a gradual (4-5-week latency) release of response suppression during punished periods over the course of several weeks of testing. This anxiolytic-like effect was still present 3 weeks following drug discontinuation. In contrast, chronic imipramine (dose regimen increase from 4 to 16 mg/kg/day), maprotiline (4 to 16 mg/kg/day), phenelzine (2 to 4 mg/kg/day), and fluoxetine (1 or 8 mg/kg/day; constant dose), resulted in no change in punished responding, suggesting that no anxiolytic-like effect developed in the course of chronic treatment with these compounds. The largest dose of all antidepressants studied (except fluoxetine) induced a moderate to marked reduction of nonpunished performance that disappeared within 1 week after the last injection. A transient release of conditioned response suppression emerged during the week that followed discontinuation of imipramine, maprotiline, and fluoxetine (8 mg/kg/day). This apparent anxiolytic-like activity might be due to a reduction of some adverse effect induced by the high doses used, and/or might have resulted from a new dynamic equilibrium between monoamine release, reuptake processes, and sensitivity of postsynaptic receptors. In conclusion, operant conflict procedures in rats seem not particularly able to model human anxiety sensitive to chronic antidepressant treatments.

Animals↗
PubMed1999

Cellular and subcellular localization of 5-hydroxytryptamine1B receptors in the rat central nervous system: immunocytochemical, autoradiographic and lesion studies.

The localization of 5-hydroxytryptamine1B receptors in the rat central nervous system was investigated using anti-peptide antibodies that recognize a selective portion of the third intracytoplasmic loop of the receptor protein. At the light microscope level the densest 5-hydroxytryptamine1B receptor-like immunoreactivity was observed in ventral pallidum, globus pallidus, substantia nigra and dorsal subiculum. In addition, moderate immunoreactivity was found in the entopeduncular nucleus, the superficial gray layer of the superior colliculus, the caudate-putamen and the deep nuclei of the cerebellum. This distribution matched perfectly that previously described from radioligand binding studies. At the ultrastructural level, 5-hydroxytryptamine1B receptor-like immunoreactivity was associated with axons and axon terminals in the three areas examined: substantia nigra, globus pallidus and superficial gray layer of the superior colliculus. In all cases, immunostaining was located on the plasma membrane of unmyelinated axon terminals and in the cytoplasm close to the plasmalemma. Synaptic differentiations were never labelled but, in some cases, 5-hydroxytryptamine1B receptor-like immunoreactivity was found in their close vicinity. Injection of kainic acid into the neostriatum resulted in a marked decrease in receptor-like immunoreactivity in the globus pallidus and the substantia nigra, consistent with the location of 5-hydroxytryptamine1B receptors on terminals of striatopallidal and striatonigral fibres, respectively. A reduction in 5-hydroxytryptamine1B receptor-like immunoreactivity was also noted in the superficial gray layer of the superior colliculus after contralateral enucleation, as expected of the location of 5-hydroxytryptamine1B receptors on the terminals of retinocollicular fibres. In both lesion experiments, immunolabelled degenerating terminals were observed in the projection areas. Anterograde labelling experiments coupled with immunocytochemical detection further showed that 5-hydroxytryptamine1B receptors in the substantia nigra are located on axons of striatal neurons. These data provide anatomical support for the idea that 5-hydroxytryptamine1B receptors act as terminal receptors involved in presynaptic regulation of the release of various neurotransmitters, including 5-hydroxytryptamine itself.

Animals↗
PubMed1999

Rapid eye movement sleep induction by vasoactive intestinal peptide infused into the oral pontine tegmentum of the rat may involve muscarinic receptors.

In rats, rapid eye movement sleep can be induced by microinjection of either the cholinergic agonist carbachol or the neuropeptide vasoactive intestinal peptide into the oral pontine reticular nucleus. Possible involvement of cholinergic mechanisms in the effect of vasoactive intestinal peptide was investigated using muscarinic receptor ligands. Sleep-waking cycles were analysed after infusion into the oral pontine reticular nucleus of vasoactive intestinal peptide (10 ng in 0.1 microl), carbachol (20 ng), atropine (200 ng) and pirenzepine (50, 100 ng), performed separately or in combination at 15-min intervals. The increase in rapid eye movement sleep due to the combined infusion of vasoactive intestinal peptide and carbachol (+58.7+/-4.6% for 8 h, P<0.05) was not significantly different from that induced by each compound separately. The enhancement of rapid eye movement sleep by vasoactive intestinal peptide was totally prevented by infusion of atropine, but not pirenzepine, a relatively selective M1 antagonist. On their own, none of the latter two compounds affected the sleep-waking cycle. Quantitative autoradiographic studies using [3H]quinuclidinyl benzylate (1 nM) and pirenzepine (0.5 microM) indicated that muscarinic receptors correspond to pirenzepine-insensitive binding sites in the oral pontine reticular nucleus. In vitro, vasoactive intestinal peptide (1-100 nM) significantly increased (+30-40%) the specific binding of [3H]quinuclidinyl benzylate to the oral pontine reticular nucleus in rat brain sections. This effect appeared to be due to an increased density, with no change in affinity, of pirenzepine-insensitive binding sites in this area. These data suggest that pirenzepine-insensitive muscarinic binding sites are involved in the induction of rapid eye movement sleep by vasoactive intestinal peptide at the pontine level in the rat.

Animals↗
PubMed1999

Differential effects of stress on presynaptic and postsynaptic 5-hydroxytryptamine-1A receptors in the rat brain: an in vitro electrophysiological study.

Extracellular and intracellular recording techniques were used to assess possible changes in the functional properties of 5-hydroxytryptamine-1A receptors in brain slices prepared from rats subjected to different stress paradigms. Whereas a 30-min restraint stress did not alter the inhibitory influence of ipsapirone on the firing of serotoninergic neurons in the dorsal raphe nucleus, the same session followed by a 24-h isolation produced a significant decrease in the potency of the 5-hydroxytryptamine-1A agonist to inhibit the electrical activity of these cells. Similarly, exposure of the animals to novel uncontrolled environmental conditions for 16 h significantly reduced the potency of ipsapirone to decrease the firing rate of serotoninergic neurons in brain stem slices. The effects of the latter two stressful paradigms were observed in slices from intact rats, but not in those from adrenalectomized animals. Intracellular recording showed that exposure of the animals to novel uncontrolled environmental conditions markedly reduced the potency of 5-carboxamidotryptamine to hyperpolarize serotoninergic neurons in the dorsal raphe nucleus and to decrease the input resistance of their plasma membrane. In contrast, the same stressful paradigm exerted no significant influence on the membrane effects of this 5-hydroxytryptamine-1A agonist on pyramidal cells in the CA1 hippocampal area. These data show that, like the direct application of corticosterone on to brain slices [Laaris N. et al. (1995) Neuropharmacology 34, 1201-1210], the stress-induced in vivo elevation of serum levels of endogenous corticosterone is associated with desensitization of somatodendritic 5-hydroxytryptamine-1A receptors in the dorsal raphe nucleus. The differential changes in 5-hydroxytryptamine-1A receptor sensitivity due to stress in the latter area versus the hippocampus further support the idea that somatodendritic and postsynaptic 5-hydroxytryptamine-1A receptors are regulated differently in the rat brain.

Animals↗
PubMed1999

Immunocytochemical evidence of vesicular localization of the orphan transporter RXT1 in the rat spinal cord.

Rxt1, a member of the Na+/Cl- orphan transporter family, exhibits numerous features suggesting a role as plasma membrane transporter. Despite numerous attempts, its substrate has not yet been identified, although immunocytochemical studies have shown that Rxt1 distribution generally matches that of glutamate or GABA. In order to further characterize Rxt1, its detailed immunocytochemical distribution in the rat spinal cord and dorsal root ganglia was studied at both light microscope and ultrastructural levels. The widespread distribution of Rxt1 in spinal cord and ganglia cannot be correlated with any known classical or peptidergic transmitter. Rxt1 is expressed in a subpopulation of glutamatergic primary afferent fibers, in large and medium-sized ganglion cells, while small glutamate cells exhibit generally no Rxt1-like immunoreactivity. In the spinal cord, Rxt1-immunoreactive cell body distribution is quite ubiquitous since Rxt1 is expressed in all laminae in various neuronal types like interneurons, some projection neurons and motoneurons. Some of these neurons are cholinergic. At the electron microscope level, the peroxidase labeling was never localized to the plasma membrane, but rather associated with different organelles including the outer membrane of small synaptic vesicles and large granular vesicles. This localization resembles that of vesicular transporters detected with the same method and suggests that Rxt1, in contrast to other Na+/Cl- transporters, is expressed on vesicles. This was confirmed using a pre-embedding silver-intensified colloidal gold method. Indeed, most gold particles appeared to be localized into the axoplasm on synaptic vesicle accumulations; only few gold particles were observed close to the plasma membrane. These results suggest that Rxt1, despite its molecular characteristics predicting a plasma membrane localization, might be a vesicular transporter.

Animals↗
PubMed1999

Anxiogenic-like effects and reduced stereological counting of immunolabelled 5-hydroxytryptamine6 receptors in rat nucleus accumbens by antisense oligonucleotides.

The physiological role of 5-hydroxytryptamine6 receptors in the central nervous system has not yet been elucidated. The high affinity of various psychotropic drugs for 5-hydroxytryptamine6 receptors has led to the suggestion that this receptor type may be a novel target in neuropsychiatry. We have found that continuous intracerebroventricular administration of a 5-hydroxytryptamine6 receptor antisense oligonucleotide, but not of a missense oligonucleotide, produced an anxiogenic-like response in rats using two different models of anxiety, the social interaction test and the elevated plus-maze. Neither oligonucleotide treatment modified locomotor activity, rectal temperature or food intake, suggesting a low or null neurotoxicity. The effectiveness of the treatment with the designed antisense oligonucleotide to block the synthesis of the protein encoded by the target mRNA was assessed by immunolabelling 5-hydroxytryptamine6 receptors in the nucleus accumbens, where this receptor is highly expressed, using previously characterized specific antibodies. The density of the immunostaining was quantified by means of an unbiased three-dimensional stereologic procedure, which revealed a significant reduction (-25%) in the number of immunolabelled neuronal elements. These results suggest that, in addition to other 5-hydroxytryptamine receptor subtypes, 5-hydroxytryptamine6 receptors in the nucleus accumbens may participate in anxiety-related neurobiological mechanisms.

Animals↗
PubMed1999

Antibodies and antisense oligonucleotide for probing the distribution and putative functions of central 5-HT6 receptors.

Among the recently cloned serotonin (5-hydroxytryptamine, 5-HT) receptors, the 5-HT6 subtype is of special interest for at least two reasons: 1) it is abundant in limbic areas which participate in the control of mood and emotion; and 2) some antidepressants and antipsychotics are potent 5-HT6 receptor antagonists. Studies using polyclonal anti-5-HT6 receptor antibodies and an antisense oligonucleotide were performed in order to investigate further the function(s) of 5-HT6 receptors in the rat brain. Immunocytochemistry at the light and electron microscope levels showed that 5-HT6 receptors are mainly confined to the dendritic compartment, suggesting that they could mediate 5-HT actions on neuronal firing. In some limbic areas, 5-HT6 receptor-like immunoreactivity is also associated with neuronal cilia with yet unknown functions. Continuous i.c.v. infusion with an antisense oligonucleotide for 3-4 days resulted in decreased 5-HT6 receptor-like immunostaining of the nucleus accumbens and anxiogenic behaviours in the social interaction and elevated plus maze tests. Selective 5-HT6 receptor ligands are eagerly expected to investigate further the potential implication of these receptors in limbic-dependent behaviours.

Amino Acid Sequence↗
PubMed1999

Unexpected localization of the Na+/Cl--dependent-like orphan transporter, Rxt1, on synaptic vesicles in the rat central nervous system.

Numerous features of its primary structure demonstrate that the orphan transporter Rxt1 belongs to the Na+/Cl--dependent neurotransmitter plasma membrane transporter superfamily, which includes the dopamine, norepinephrine, serotonin and gamma-aminobutyric acid (GABA) transporters. Initial immunocytochemical investigations with affinity-purified antibodies have established that Rxt1 is localized, almost exclusively, in axon terminals of glutamatergic neurons and subsets of GABAergic neurons in the CNS. Further studies were carried out to determine its subcellular distribution. In a first series of experiments, PC-12 cells were transfected with plasmids encoding either the dopamine transporter or Rxt1. Immunofluorescence experiments showed that the dopamine transporter was expressed in these cells, and, as expected, addressed to their plasma membrane. Surprisingly, this was never the case with Rxt1, which was targeted to the same subcellular compartment as synaptophysin, a vesicular protein. In a second set of experiments, subcellular fractionation of rat striatum showed that Rxt1, but not the dopamine transporter, was relatively abundant in the purified synaptic vesicle fraction. Finally, electron microscopic immunocytochemistry with anti-Rxt1 antibodies showed peroxidase as well as pre- and post-embedding immunogold labelling confined to the intracellular compartment in various brain regions. Moreover, quantitative analysis of post-embedding experiments demonstrated that the immunogold particles corresponding to Rxt1 immunoreactivity were mostly localized to small synaptic vesicles. These data indicate that, in contrast with the other members of the Na+/Cl--dependent neurotransmitter transporter superfamily, which are targeted to the plasma membrane, Rxt1 is distributed as a vesicular protein in the CNS.

Animals↗
PubMed1999

5-HT1A and 5-HT1B receptors control the firing of serotoninergic neurons in the dorsal raphe nucleus of the mouse: studies in 5-HT1B knock-out mice.

The characteristics of the spontaneous firing of serotoninergic neurons in the dorsal raphe nucleus and its control by serotonin (5-hydroxytryptamine, 5-HT) receptors were investigated in wild-type and 5-HT1B knock-out (5-HT1B-/-) mice of the 129/Sv strain, anaesthetized with chloral hydrate. In both groups of mice, 5-HT neurons exhibited a regular activity with an identical firing rate of 0.5-4.5 spikes/s. Intravenous administration of the 5-HT reuptake inhibitor citalopram or the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induced a dose-dependent inhibition of 5-HT neuronal firing which could be reversed by the selective 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xane carboxamide (WAY 100635). Both strains were equally sensitive to 8-OH-DPAT (ED50 approximately 6.3 microgram/kg i.v.), but the mutants were less sensitive than wild-type animals to citalopram (ED50 = 0.49 +/- 0.02 and 0.28 +/- 0.01 mg/kg i.v., respectively, P < 0.05). This difference could be reduced by pre-treatment of wild-type mice with the 5-HT1B/1D antagonist 2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carbox yli c acid [4-methoxy-3-(4-methyl-piperazine-1-yl)-phenyl]amide (GR 127935), and might be accounted for by the lack of 5-HT1B receptors and a higher density of 5-HT reuptake sites (specifically labelled by [3H]citalopram) in 5-HT1B-/- mice. In wild-type but not 5-HT1B-/- mice, the 5-HT1B agonists 3-(1,2,5, 6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94253, 3 mg/kg i.v.) and 5-methoxy-3-(1,2,3, 6-tetrahydropyridin-4-yl)-1H-indole (RU 24969, 0.6 mg/kg i.v.) increased the firing rate of 5-HT neurons (+22.4 +/- 2.8% and +13.7 +/- 6.0%, respectively, P < 0.05), and this effect could be prevented by the 5-HT1B antagonist GR 127935 (1 mg/kg i.v.). Altogether, these data indicate that in the mouse, the firing of 5-HT neurons in the dorsal raphe nucleus is under both an inhibitory control through 5-HT1A receptors and an excitatory influence through 5-HT1B receptors.

Animals↗
PubMed1999

Long-term enhancement of REM sleep by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in the pontine reticular formation of the rat.

In rats, rapid eye movement (REM) sleep can be elicited by microinjection of vasoactive intestinal polypeptide (VIP) into the oral pontine reticular nucleus (PnO). In the present study, we investigated whether this area could also be a REM-promoting target for a peptide closely related to VIP: the pituitary adenylyl cyclase-activating polypeptide (PACAP). When administered into the posterior part of the PnO, but not in nearby areas, of freely moving chronically implanted rats, PACAP-27 and PACAP-38 (0.3 and 3 pmol) induced a marked enhancement (60-85% over baseline) of REM sleep for 8 h that could be prevented by prior infusion of the antagonist PACAP-(6-27) (3 pmol) into the same site. Moreover, injections of PACAP into the centre of the posterior PnO resulted in REM sleep enhancement which could last for up to 11 consecutive days. Quantitative autoradiography using [125I]PACAP-27 revealed the presence in the PnO of specific binding sites with high affinity for PACAP-27 and PACAP-38 (IC50 = 2.4 and 3.2 nM, respectively), but very low affinity for VIP (IC50 > 1 microM). These data suggest that PACAP within the PnO may play a key role in REM sleep regulation, and provide evidence for long-term (several days) mechanisms involved in such a control. PAC1 receptors which have a much higher affinity for PACAP than for VIP might mediate this long-term action of PACAP on REM sleep.

Animals↗
PubMed1999

The "orphan" Na+/Cl(-)-dependent transporter, Rxt1, is primarily localized within nerve endings of cortical origin in the rat striatum.

Previous studies have shown that the striatum expresses very low levels of Na+/Cl(-)-dependent "orphan" transporter Rxt1 transcripts but contains high levels of protein. This study investigated the origin of Rxt1 expression in rat striatum. Striatal Rxt1 contents assessed by immunocytochemistry or western blotting were found to be significantly reduced after corticostriatal denervation but not after striatal or thalamic lesion with kainic acid or selective 6-hydroxydopamine-induced nigrostriatal deafferentation. Corticostriatal neurons retrogradely labeled by intrastriatal fluorogold injections were shown to express Rxt1 mRNA. Combination of anterograde biotin-dextran amine labeling of the corticostriatal pathway with Rxt1 immunogold detection at the ultrastructural level demonstrated the presence of Rxt1 in about one-third of the corticostriatal synaptic terminals and in numerous unidentified synaptic terminals. All the Rxt1-positive terminals formed asymmetrical contacts on spines. These data provide evidence that striatal Rxt1 immunoreactivity is mainly of extrinsic origin and more specifically associated with the corticostriatal pathway. Rxt1 appears as a selective presynaptic marker of synapses formed by presumably excitatory amino acid afferents, but it segregates a subclass of these synapses, thereby revealing a functional heterogeneity among excitatory amino acid systems.

Afferent Pathways↗
PubMed1999

Effects of peripheral axotomy on cholecystokinin neurotransmission in the rat spinal cord.

Because cholecystokinin (CCK) acts as a "functional" endogenous opioid antagonist, it has been proposed that changes in central CCKergic neurotransmission might account for the relative resistance of neuropathic pain to the analgesic action of morphine. This hypothesis was addressed by measuring CCK-related parameters 2 weeks after unilateral sciatic nerve section in rats. As expected, significant decreases (-25-38%) in the tissue concentrations and in vitro release of both substance P and calcitonin gene-related peptide were noted in the dorsal quadrant of the lumbar spinal cord on the lesioned side. In contrast, the tissue levels and in vitro release of CCK were unchanged in the same area in lesioned rats. Measurements in dorsal root ganglia at L4-L6 levels revealed no significant changes in proCCK mRNA after the lesion. However, sciatic nerve section was associated with a marked ipsilateral increase in both CCK-B receptor mRNA levels in these ganglia (+70%) and the autoradiographic labeling of CCK-B receptors by [3H]pBC 264 (+160%) in the superficial layers of the lumbar dorsal horn. Up-regulation of CCK-B receptors rather than CCK synthesis and release probably contributes to increased spinal CCKergic neurotransmission in neuropathic pain.

Animals↗
PubMed1999

[Coronary stents].

Coronary stents are widely used in percutaneous revascularisation and are associated with excellent primary results in the majority of cases. The anti GPIIb/IIIa molecules and the association of ticlopidine and aspirin are part of the pharmacological environment which contributes to the short-term success of these procedures. The essential problem remains restenosis which, in its diffuse form, is difficult to treat. Physicians should be vigilant with respect to the quality of the stents which they use and should enforce the conditions which the working group of the European Society of Cardiology recently proposed. Finally, in indications not yet validated or in the process of validation, they should be very careful and good results of balloon angioplasty should be respected.

Angioplasty, Balloon, Coronary↗
PubMed1998

Hearing loss due to the mitochondrial A1555G mutation in Italian families.

Six Italian families with familial nonsyndromic hearing loss consistent with a maternal pattern of inheritance were analyzed for mitochondrial mutations. The three known mitochondrial mutations associated with nonsyndromic hearing loss were investigated by polymerase chain reaction amplification, followed by restriction fragment length analysis or DNA sequencing. The A7445G mutation and C7472 insertion were not present in either of the families, but the A1555G mutation in the 12S rRNA gene was identified in homoplasmic form in two of the families. In one of the families the onset of hearing loss is congenital, while in the other it starts later in life. The families are from different regions of Italy, and mitochondrial haplotype analysis showed that the mutation arose independently in these two families. This suggests that the A1555G mutation may not be an uncommon cause of hearing loss in Italians, and is clinically important because maternal hearing relatives of patients with the A1555G mutation are at risk for aminoglycoside induced deafness. We discuss potential reasons for the normal phenotype in some relatives with the mutation, and the different onset of hearing loss in the two families.

Adolescent↗