RESUMO
During the COVID-19 pandemic, surgical elective procedures were stopped in our plastic surgery unit. Limitations for consultations and for follow-up of previous surgical procedures were imposed in order to minimize the risk of contagion in waiting rooms and outpatient clinics. We have identified telemedicine as an alternative way to follow patients during the lockdown. Nevertheless, we have experienced different difficulties. We have not had the possibility to use a secure teleconferencing software. In our unit we had not technological devices. Surgeons in our department were not able to use remote video technology for patient management. Guidelines for an appropriate selection of patients which could be served via telemedicine had to be created. Telemedicine must be regulated by healthcare organizations for legal, ethical, medico-legal and risk management aspects. Even if we have experienced an important need to use telematic solutions during the COVID-19 lockdown, liability and risk management issues has greatly limited this possibility in our unit. The need of telemedicine in the time of COVID-19 pandemic has encouraged us to implement future virtual encounters in order to reduce unnecessary in-person visits by taking into consideration all legal, ethical and medico-legal aspects.
Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Procedimentos de Cirurgia Plástica/métodos , Pneumonia Viral/epidemiologia , Gestão de Riscos/métodos , Cirurgia Plástica/organização & administração , Telemedicina/métodos , COVID-19 , Infecções por Coronavirus/transmissão , Humanos , Pandemias , Pneumonia Viral/transmissão , SARS-CoV-2RESUMO
Microdeletion of chromosome 22q13.31 is a very rare condition. Fourteen patients have been annotated in public databases but, to date, a clinical comparison has not been done and, consequently, a specific phenotype has not been delineated yet. We describe a patient showing neurodevelopmental disorders, dysmorphic features, and multiple congenital anomalies in which SNP array analysis revealed an interstitial 3.15 Mb de novo microdeletion in the 22q13.31 region encompassing 21 RefSeq genes and seven non-coding microRNAs. To perform an accurate phenotype characterization, clinical features observed in previously reported cases of 22q13.31 microdeletions were reviewed and compared to those observed in our patient. To the best of our knowledge, this is the first time that a comparison between patients carrying overlapping 22q13.31 deletions has been done. This comparison allowed us to identify a distinct spectrum of clinical manifestations suggesting that patients with a de novo interstitial microdeletion involving 22q13.31 have an emerging syndrome characterized by developmental delay/intellectual disability, speech delay/language disorders, behavioral problems, hypotonia, urogenital, and hands/feet anomalies. The microdeletion identified in our patient is the smallest reported so far and, for this reason, useful to perform a detailed genotype-phenotype correlation. In particular, we propose the CELSR1, ATXN10, FBLN1, and UPK3A as candidate genes in the onset of the main clinical features of this contiguous gene syndrome. Thus, the patient reported here broadens our knowledge of the phenotypic consequences of 22q13.31 microdeletions facilitating genotype-phenotype correlations. Additional cases are needed to corroborate our hypothesis and confirm genotype-phenotype correlations of this emerging syndrome.
Assuntos
Transtornos Cromossômicos/genética , Deficiências do Desenvolvimento/genética , Transtornos do Neurodesenvolvimento/genética , Adolescente , Ataxina-10/genética , Caderinas/genética , Proteínas de Ligação ao Cálcio/genética , Deleção Cromossômica , Transtornos Cromossômicos/fisiopatologia , Cromossomos Humanos Par 22/genética , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/fisiopatologia , Estudos de Associação Genética , Humanos , Masculino , Transtornos do Neurodesenvolvimento/fisiopatologia , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Uroplaquina III/genéticaRESUMO
Non-recurrent microdeletion (≤2â¯Mb in size) in 7p22.1 is a rarely described cytogenetic aberration, only recently reported in patients with developmental delay/intellectual disability, short stature and microcephaly. The size of the deletions ranged from 0.37 to 1.5â¯Mb, and reported genotype-phenotype correlations identified a minimum deleted region of 0.37â¯Mb involving the FBLX18, ACTB, FSCN1, RNF216 and ZNF815P genes. The authors suggested that deletion of ACTB, which encodes ß-actin, an essential component of the cytoskeleton, could be responsible for the clinical features observed in the patients with a 7p22.1 microdeletion. Here, we describe a 23-month-old child displaying developmental delay, short stature, microcephaly and distinctive facial features. Chromosomal microarray analysis performed using high-resolution SNP-array platform revealed a de novo interstitial 60â¯Kb microdeletion in the 7p22.1 region (from 5,509,127 bp to 5,569,096 bp, hg19) encompassing only two genes: FBXL18 and ACTB. To the best of our knowledge, this is the smallest deletion at 7p22.1 to date reported in medical literature (Pubmed). Combining our data with phenotypic and genotypic data of cases from literature, we were able to narrow the minimal critical region, which contained only two genes, i.e., FBXL18 and ACTB. Our finding is useful to perform a more accurate genotype-phenotype correlation and strongly strengthen the hypothesis that haploinsufficiency of ACTB is the main cause of the clinical phenotype observed in the patients with 7p22.1 microdeletions, facilitating genetic diagnosis and counseling.
Assuntos
Actinas/genética , Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Anormalidades Craniofaciais/patologia , Deficiências do Desenvolvimento/patologia , Feminino , Haploinsuficiência , Humanos , Lactente , Fenótipo , SíndromeRESUMO
INTRODUCTION: Safety Surgery CheckList (SSCL) is a support tool for operating teams, used to carry out safety checks while also encouraging compliance with the implementation of recommended quality and safety standards. In Emilia-Romagna it was deemed appropriate to check actual surgical team compliance with correct checklist application in the operating theatre, through a project called "OssERvare". METHODS: Direct observation was identified as the preferred inspection method. With the use of special report sheets, observers proceeded with the guided observation of behaviour in the operating room, recording any inconsistencies with correct SSCL use methods. The project began in January 2017 and all observations were carried out from 1st January-15th April 2017. RESULTS: In 43% of observed operation sign in, all three team members were not present, whereas in 7% of observed cases, sign out was not carried out. All three team members were present in 88% of observed operation time out. There are two evidently critical phases: sign in and sign out. Results obtained for time out were better. DISCUSSION AND CONCLUSION: Compliance data collected from observations differed markedly from reported compliance in administrative flow records. The results of the observational study indicate that the SSCL is not properly filled in many times; there is also a great possibility to improve the correct use of this tool. In conclusion, we think that the combined approach of use of administrative data and assessing compliance appeared to be a useful instrument to investigate the implementation and to promote the real utilization of safety tools such as the SSCL.
Assuntos
Salas Cirúrgicas/normas , Equipe de Assistência ao Paciente/organização & administração , Procedimentos Cirúrgicos Operatórios/normas , Lista de Checagem , Humanos , Equipe de Assistência ao Paciente/normas , Segurança do PacienteRESUMO
Post-myocardial infarction (MI) ventricular septal defects (VSD) are a rare but life-threatening complication of acute MI, with very high mortality rates even if timely approached by surgical repair. Transcatheter closure is an attractive alternative to surgery. However, this option is currently deemed challenging and often unsuitable in complex VSD. We report the case of a young woman in poor hemodynamic conditions due to a complex post-MI VSD. A two-step percutaneous VSD closure was successfully performed adopting a patient-tailored approach based on a throughout knowledge of the anatomic and functional picture using both commercially available dedicated and off-label devices.
Assuntos
Comunicação Interventricular/cirurgia , Dispositivo para Oclusão Septal , Feminino , Comunicação Interventricular/etiologia , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Implantação de Prótese/métodosRESUMO
The paper describes a putative digenic form of deafness in two siblings affected by non-syndromic hereditary hearing loss, detected by a Targeted resequencing approach. Given that a previous paper suggested TMPRSS3 and GJB2 genes as responsible for a digenic form of hearing loss, our data support and reinforce this hypothesis.
Assuntos
Conexinas/genética , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Serina Endopeptidases/genética , Adolescente , Criança , Conexina 26 , Feminino , Perda Auditiva Neurossensorial/fisiopatologia , Heterozigoto , Humanos , Masculino , Mutação , Análise de Sequência de DNA , IrmãosRESUMO
We report on a patient with psychomotor deficits, language delay, dyspraxia, skeletal anomalies, and facial dysmorphisms (hirsutism, right palpebral ptosis, a bulbous nasal tip with enlarged and anteverted nares, and a mild prominent antihelix stem). Using high-resolution SNP array analysis, we identified a 0.49-Mb microduplication in chromosome 6q26 inherited from the mother involving the PARK2 gene: arr[hg19] 6q26(162,672,821-163,163,143)×3 mat. To the best of our knowledge, this is the third patient to date described in whom a 6q26 microduplication encompassing only the PARK2 gene has been reported in medical literature. The PARK2 gene is a neurodevelopmental gene that was initially discovered as one of the causes of autosomal recessive juvenile Parkinson disease and subsequently reported to be linked to autism spectrum disorders and attention-deficit hyperactivity disorders. We provide an overview of the literature on PARK2 microduplications and further delineate the associated phenotype. Taken together, our findings confirm the involvement of this gene in neurodevelopmental disorders and are useful to strengthen the hypothesis that, although with variable expressivity and incomplete penetrance, the PARK2 microduplication is associated with a new emerging neurodevelopmental delay syndrome. However, clinical and molecular evaluations of more patients with the microduplication are needed for full delineation of this syndrome.
RESUMO
Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe genetic disorder arising in the perinatal period, although a late-onset presentation of the disease has been described. Pulmonary hypoplasia is the major cause of morbidity and mortality in the newborn period. ARPKD is caused by mutations in the PKHD1 (polycystic kidney and hepatic disease 1) gene that is among the largest human genes. To achieve a molecular diagnosis of the disease, a large series of Italian affected subjects were recruited. Exhaustive mutation analysis of PKHD1 gene was carried out by Sanger sequencing and multiple ligation probe amplification (MLPA) technique in 110 individuals. A total of 173 mutations resulting in a detection rate of 78.6% were identified. Additional 20 unrelated patients, in whom it was not possible to analyze the whole coding sequence, have been included in this study. Taking into account the total number (n=130) of this cohort of patients, 107 different types of mutations have been detected in 193 mutated alleles. Out of 107 mutations, 62 were novel: 11 nonsense, 6 frameshift, 7 splice site mutations, 2 in-frame deletions and 2 multiexon deletion detected by MLPA. Thirty-four were missense variants. In conclusion, our report expands the spectrum of PKHD1 mutations and confirms the heterogeneity of this disorder. The population under study represents the largest Italian ARPKD cohort reported to date. The estimated costs and the time invested for molecular screening of genes with large size and allelic heterogeneity such as PKHD1 demand the use of next-generation sequencing (NGS) technologies for a faster and cheaper screening of the affected subjects.
Assuntos
Mutação , Rim Policístico Autossômico Recessivo/genética , Receptores de Superfície Celular/genética , Adolescente , Adulto , Alelos , Substituição de Aminoácidos , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Rim Policístico Autossômico Recessivo/diagnóstico , Análise de Sequência de DNA , Adulto JovemRESUMO
BACKGROUND: Structural rearrangements of chromosome 19p13.3 are a rare condition, and their phenotypic consequences remain not well defined, because of the variability of clinical manifestations. Increasing knowledge of new 19p13.3 microdeletion is useful to clarify the phenotypic variability observed in some patients. In a small number of recent papers, patients with intellectual disabilities, multiple congenital anomalies and microdeletion of the chromosome band 19p13.3 have been described. However, little is known about genes responsible for clinical features in patients carriers of 19p13.3 microdeletion; thus, increasing number of reported cases will be helpful to investigate the contribution of candidate genes, providing bases for future investigations. CASE PRESENTATION: Here, we report on a 10-years-old girl referred to our genetics clinic due to intellectual disability, attention deficit, behavioral and speech delay, hypotonia, facial dysmorphisms, eye anomalies and congenital malformations. Using an high resolution SNP array, we identified a de novo microdeletion of chromosome 19p13.3, resulting in the heterozygous loss of 27 RefSeq genes and a miRNA, partially overlapping with three others deletions already reported in literature, but extending downstream (centromeric) for additional 386 Kb. This chromosomal region includes 13 genes amongst of which we suggest for the first time the APC2, PLK5 and MBD3 genes as potential functional candidates for neurodevelopmental and behavioral phenotypes observed. CONCLUSIONS: Here we describe a patient with a 19p13.3 microdeletion that spans to the downstream chromosomal region with respect to the overlapping deletions previously reported in several other cases. The neurobehavioral features observed in our case has extended the phenotypic spectrum associated with the 19p13.3 microdeletion. New candidate genes are proposed for the neurobehavioral phenotype observed in our case.
RESUMO
We provide a detailed clinical and molecular characterization of an 11-year-old female patient presenting with neurodevelopmental delay (NDD), intellectual disability (ID), seizures, stereotypies and dysmorphic features. Chromosomal microarrays analysis (CMA) detected a small, rare de novo deletion on chromosome 12q24.31 encompassing 31 protein-coding RefSeq genes and a microRNA. Phenotypic comparison with molecularly well-defined cases previously reported in the literature harboring an overlapping 12q24.31 microdeletion indicate that these patients shared common clinical features including neurodevelopmental delay, intellectual disability and behavioral problems. Also, seizures and dysmorphic features are frequent and a consistent pattern was recognized. Since there are remarkable resemblance between the patient described here and at least another one previously reported, our report is provides supportive evidence for the existence of an emerging syndrome caused by a microdeletion in 12q24.31. We propose a minimal region shared among patients contributing to the etiology of the common clinical features observed suggesting as candidate, for the first time, the gene SETD1B which is a component of a histone methyltransferase complex. In addition, we speculate on the possible contributive role of the MIR4304 to some clinical features observed in our patient. Evaluation of more patients with well-characterized deletions within 12q24.31, as well as careful clinical assessment of them, is needed to corroborate our hypothesis, to perform a more detailed genotype-phenotype correlation and, finally, to fully delineate this emerging microdeletion syndrome.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 12 , Ossos Faciais/anormalidades , Deficiência Intelectual/genética , Convulsões/genética , Comportamento Estereotipado , Pré-Escolar , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Fácies , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Fenótipo , Convulsões/diagnósticoRESUMO
BACKGROUND: Inactivating mutations of the calcium-sensing receptor (CaSR), of the G-protein subunit α11 (GNA11) and of the adaptor-related protein complex 2, sigma 1 subunit (AP2S1) genes are responsible for familial hypocalciuric hypercalcaemia (FHH). The aim of this study was to analyse prevalence and pathogenicity of CaSR, GNA11 and AP2S1 mutations in patients with an FHH phenotype and to compare them with a sample of patients with primary hyperparathyroidism (PHPT) in order to identify the most useful laboratory parameter for a differential diagnosis. METHODS: Patients with an FHH phenotype were studied with polymerase chain reaction amplification and direct sequencing of the entire CaSR, GNA11 and AP2S1 coding sequences. Novel mutations were introduced in a Myc-tagged human wild-type (WT) CaSR cDNA-expressing vector, and functional assay was performed on human embryonic kidney cells evaluating expression and function of mutated proteins. RESULTS: Among 16 FHH patients, none had an inactivating GNA11 or AP2S1 mutation while 3 (18.8%) carried a CaSR mutation and 10 (62.5%) at least one CaSR polymorphism. Within the latter group, 7 of 10 patients had more than one polymorphism (4.1 ± 2.1 per patient). Two novel CaSR mutations [c.2120A>T (E707V) and c.2320G>A (G774S)] were identified: the E707V mutation prevented CaSR expression (western blot), whereas the G774S mutation determined a reduced receptor sensitivity to calcium (IP3 assay). PHPT patients showed significantly (P < 0.001) higher serum calcium, parathyroid hormone, urinary calcium and calcium-creatinine clearance ratio (CCCR) and significantly lower serum phosphate than FHH ones. CONCLUSIONS: FHH should be clearly differentiated by PHPT to avoid unnecessary surgery: CCCR could be a useful screening tool while genetic analysis should include the two novel CaSR mutations herein described. The role of multiple polymorphisms deserves further investigation in patients with an FHH phenotype.
Assuntos
Hipercalcemia/congênito , Hiperparatireoidismo Primário/genética , Mutação/genética , Polimorfismo Genético/genética , Receptores de Detecção de Cálcio/genética , Complexo 2 de Proteínas Adaptadoras/genética , Subunidades sigma do Complexo de Proteínas Adaptadoras/genética , Adulto , Idoso , Western Blotting , Estudos de Coortes , DNA/genética , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/genética , Hiperparatireoidismo Primário/diagnóstico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Detecção de Cálcio/metabolismoRESUMO
Interstitial deletion of chromosome region 3p14.1, including FOXP1 gene, is relatively rare and, until recently, there were no strong evidences to support the hypothesis that this microdeletion could play a role in the etiology of genomic disorders. Here, we report on an adult patient with a recognizable phenotype of autism, severe speech delay, deficit of motor coordination and typical dysmorphic features. Analysis of a dense whole genome single-nucleotide polymorphism (SNP) array showed a 1Mb interstitial deletion of chromosome region 3p14.1 including the entire coding region of FOXP1 (MIM 605515) gene. In order to study the parental origin of the deletion, we analyzed selected SNPs in the deleted area in the proband and his parents showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of paternal origin. Despite the frequency of this genomic alteration has not been estimated, our patient confirm the hypothesis that microdeletion of 3p14.1 seems to be a rare cause of cognitive disorders and that haploinsufficiency of FOXP1 may play a role in neurological and language deficits in patients carrying a 3p14.1 deletion. Finally, our patient is also important because useful to further delineate the clinical spectrum secondary to the 3p14.1 microdeletions.
Assuntos
Transtorno Autístico/genética , Fatores de Transcrição Forkhead/genética , Deleção de Genes , Transtornos do Desenvolvimento da Linguagem/genética , Proteínas Repressoras/genética , Anormalidades Múltiplas/genética , Adulto , Fatores de Transcrição Forkhead/metabolismo , Haploinsuficiência , Humanos , Cariótipo , Imageamento por Ressonância Magnética , Masculino , Atividade Motora/genética , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/metabolismo , Análise de Sequência de DNA , Adulto JovemRESUMO
CHARGE syndrome is an autosomal dominant inherited disorder characterized by a specific and recognizable pattern of anomalies. De novo mutations or deletions of the gene encoding chromodomain helicase DNA binding protein 7 (CHD7) are the major cause of CHARGE syndrome. In this report, we describe a patient with a typical phenotype characterized by psychomotor retardation, hypertrichosis, facial asymmetry, synophria, failure to thrive, developmental delay and gastro-esophageal reflux, carrying a de novo 6.04Mb interstitial deletion in 8q12.1q12.3 detected by single nucleotide polymorphism (SNP) array analysis. Despite the deletion includes CHD7 and although the patient shares some of the clinical features of the CHARGE syndrome, she does not fulfill the clinical criteria for this syndrome. To the best of our knowledge, this is the second case with an entire deletion of the CHD7 gene not leading to CHARGE syndrome and, for this reason, useful to expand and further delineate the clinical features associated with the 8q12.1q12.3 deletion. Furthermore, the literature review revealed that the phenotype secondary to duplications of the same region partially overlaps with the phenotype reported in this study. Selected genes that are present in the hemizygous state and which might be important for the phenotype of this patient, are discussed in context of the clinical features.
Assuntos
Síndrome CHARGE/genética , Cromossomos Humanos Par 8/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Deleção de Sequência , Sequência de Bases , Criança , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de DoençaRESUMO
Interstitial deletions of chromosome 15q25.2 are rare. To date, only nine patients with microdeletions within this chromosomal region have been described. Here, we report on a girl with severe speech and psychomotor delay, behavioral problems and mild dysmorphic features with a 1.6 Mb deletion in 15q25.2 region. In order to study the parental origin of the rearrangement, we analyzed selected SNPs in the deleted area in the patient and her parents, showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of maternal origin. By comparing the clinical and molecular features of our patient with five previously reported cases of an overlapping deletion, we suggest that 15q25.2 deletion is an emerging syndrome characterized by a distinct although variable spectrum of clinical manifestations, including mild dysmorphic features, neurodevelopmental delay, and a recognizable pattern of congenital malformation. Furthermore, our patient is the second one in which a behavioral phenotype characterized by hyperactivity, anxiety, and autistic features was reported, indicating that these features might be part of this new syndromic condition. Breakpoints of the deletion in the patient reported here are useful to better define the smallest region of overlap (SRO) among all the patients. Selected genes that are present in the hemizygous state and which might be important for the phenotype of these patients, are discussed in context of the clinical features. In conclusion, our patient increases the knowledge about the molecular and phenotypic consequences of interstitial 15q25.2 deletions, highlighting that deletions of this region may be responsible for a new microdeletion syndrome.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 15 , Deficiências do Desenvolvimento/genética , Deleção de Sequência , Anormalidades Múltiplas/genética , Criança , Feminino , Humanos , FenótipoRESUMO
BACKGROUND: Chromosomal imbalances, recognized as the major cause of mental retardation, are often due to submicroscopic deletions or duplications not evidenced by conventional cytogenetic methods. To date, interstitial deletion of long arm of chromosome 2 have been reported for more than 100 cases, although studies reporting small interstitial deletions involving the 2q24.1q24.2 region are rare. With the widespread clinical use of comparative genomic hybridization chromosomal microarray technology, several cryptic chromosome imbalances have outlined new genotype-phenotype correlations and isolated a number of distinctive clinical conditions. RESULTS: here we report on a girl with mental retardation and generalized hypotonia. A genome-wide screen for copy number variations (CNVs) using single nucleotide polymorphisms (SNPs) array revealed a 7.5 Mb interstitial deletion of chromosome region 2q24.1q24.2 encompassing 59 genes, which was absent in parents. The gene content analysis of the deleted region and review of the literature revealed the presence of some genes that may be indicated as good candidate in generating the main clinical features of the patient. DISCUSSION: the present case represents a further patient described in the literature with an interstitial deletion of chromosome 2q24.1q24.2. Our patient shares some clinical features with the previously reported patients carriers of overlapping 2q24 deletion. Although more cases are needed to delineate the full-blown phenotype of 2q24.1q24.2 deletion syndrome, published data and present observation suggest that hemizygosity of this region results in a clinically recognizable phenotype. Considering these clinical and cytogenetic similarities, we suggest the existence of an emerging syndrome associated to 2q24.1q24.2 region.
RESUMO
Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goitre and defective iodide organification. Congenital and profound hearing loss is the hallmark of the syndrome, while goitre and thyroid dysfunction are highly variable even within the same family. Clinical features are due to altered formation of pendrin, a chloride/iodide transporter protein expressed in the inner ear, thyroid gland and kidney. A novel substitution was found in exon 7 of the pendrin encoding gene (SLC26A4) that leads to a stop codon, S314X. The new variation was found in compound heterozygosity with L445W mutation in a hearing impaired patient with bilateral Mondini's dysplasia and goitre.
Assuntos
Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Proteínas de Membrana Transportadoras/genética , Adolescente , Feminino , Seguimentos , Bócio Nodular/diagnóstico , Bócio Nodular/genética , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Itália , Imageamento por Ressonância Magnética/métodos , Mutação , Índice de Gravidade de Doença , Transportadores de Sulfato , Tomografia Computadorizada por Raios X/métodosRESUMO
The aim of this study was to describe the clinical features of hearing loss due to mutations on connexin 26/30 coding genes (GJB2/GJB6). Mutations in the GJB2 gene are found to account for approximately 50% of cases of autosomal recessive non-syndromic deafness. Several European studies have estimated that the GJB2 healthy carrier condition involves about 2-4% of the population, with the 35delG mutations being the most common. A 342-kb deletion truncating the GJB6 gene (encoding connexin-30) has been associated with autosomal recessive non-syndromic deafness, mostly as digenic inheritance of the Cx30 deletion/Cx26 mutation. The following retrospective study describes audiological features and genotypes of a large cohort of 376 Italian hearing-impaired patients who underwent genetic screening for the GJB2/GJB6 genes and received follow-up care at our centre between January 2002 and October 2006. Sixteen different genotypes causing deafness in more than 27% of patients with either biallelic mutations or digenic inheritance GJB2/GJB6 were identified. The most frequent mutations were 35delG, M34T, L90P, and R184P.
Assuntos
Conexinas/genética , Perda Auditiva Neurossensorial/genética , Mutação , Testes de Impedância Acústica , Adolescente , Adulto , Idoso , Alelos , Audiometria de Tons Puros , Percepção Auditiva , Criança , Pré-Escolar , Estudos de Coortes , Conexina 26 , Conexina 30 , Progressão da Doença , Feminino , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/fisiopatologia , Heterozigoto , Homozigoto , Humanos , Lactente , Padrões de Herança , Itália , Masculino , Pessoa de Meia-Idade , Otoscopia , Fenótipo , Reflexo Acústico , Estudos Retrospectivos , Adulto JovemRESUMO
Nonsyndromic sensorineural hearing impairment is inherited in a predominantly autosomal recessive manner in up to 70% of cases. The gene more often involved is GJB2, encoding the gap junction protein Connexin 26. We report here a novel missense mutation in the GJB2 gene found in a Tunisian family. A homozygous change C/G at nucleotide 263 was detected in the 4-year-old girl of this family, affected by congenital moderate hearing loss. This transversion leads to the replacement of a highly conserved alanine with glycine at codon 88 (A88G). The consanguineous parents of the child are healthy carriers of the mutation.