Andrea Trevas Maciel Guerra

Molecular genetics study of deafness in Brazil: 8-year experience.

Hereditary hearing loss is a complex disorder that involves a large number of genes. In developed countries, 1 in 1,000 children is born with deafness severe enough to require special education services, and about 60% of the cases of isolated deafness have a genetic origin. Although more than 100 genes for hearing loss are known currently, only a few are routinely tested in the clinical practice. In this study, we present our findings from the molecular diagnostic screening of the GJB2 and GJB3 genes, del(GJB6‐D13S1830) and del(GJB6‐D13S1854) deletions in the GJB6 gene, Q829X mutation in the otoferlin gene (OTOF) and, the A1555G and A7445G mutations in the mitochondrial genome over an 8‐year period. Mutations analysis in the previously mentioned genes and mutations was performed on 645 unrelated Brazilian patients with hearing loss who fell into two different testing groups. Different mutations in the GJB2 gene were responsible for most of cases studied, but deletions in the GJB6 gene as well as mitochondrial mutations were also found. While most cases of hearing loss in this country are due to environmental factors, the genetic etiology of deafness will increasingly be determined as more genetic tests become available.

Cardiovascular and renal anomalies in Turner syndrome

OBJECTIVE To evaluate the frequency and type of cardiovascular (CV) and renal/collecting system (R/CS) abnormalities seen in a sample of patients with Turner Syndrome (TS) and to verify the proportion of those anomalies detected only after diagnosis was established. METHODS Retrospective study of 130 patients with TS diagnosed in an outpatient setting between 1989 and 2006. The mean age at diagnosis was 11.9 years. Data were obtained by personal history of CV and R/CS disorders and by results of echocardiogram and ultrasonography of the kidneys and collecting system performed after diagnosis. RESULTS 25.6% of patients who underwent echocardiograms presented CV abnormalities. Among them, mitral regurgitation (21.4%), bicuspid aortic valve (19%) and aortic coarctation (19%) were the most frequent. R/CS anomalies were found in 29.3% of patients who underwent ultrasonography. Among them, duplication of the collecting system and hydronephrosis (25% each) and horseshoe kidney (21.2%) were the most frequent. In about 80% of cases there was no previous knowledge of these anomalies. CONCLUSION The frequency of CV and R/CS abnormalities found in this study was similar to that of previous studies, but most were found in routine exams after TS diagnosis. Thus, early detection of associated anomalies depends on early detection of TS.

A investigação genética na surdez hereditária não-sindrômica

The precise diagnosis of hearing loss can be clarified by genetic investigation. Non-syndromic hearing loss is responsible for 70% of all genetic causes of hearing loss. More than 100 genes are potentially involved in non-syndromic hearing loss. A specific mutation (35delG) on the GJB2 gene that codifies Conexin 26 protein is the most common finding in non-syndromic hereditary hearing loss. AIM: In this study the presence of mutations 35delG, A1555G/12SeRNA and A7445G/tRNASer (UCN) where investigated for patients with hearing loss of unknown cause. STUDY DESIGN: Clinical study with transversal cohort. MATERIAL AND METHOD: 75 outpatients from the Department of Otolaryngology and Head and Neck Surgery of the University of Campinas-UNICAMP were evaluated from July to December of 2000. A total of six mutations were found, four 35delG/GJB2, one A7445G/tRNASer (UCN) and W172X/GJB2, a mutation not yet described in previous literature. CONCLUSION: The investigation of mutations associated with hearing loss can be carried out easily, elucidates the etiology and allows genetic counseling of the family.

A percepção da doença em portadoras da síndrome de Turner

OBJECTIVE: To identify how patients with Turner syndrome perceive their condition. METHODS: Thirty-six women with Turner syndrome, aged between 15 and 25 years and with over 2 years of medical follow-up, were individually interviewed about: the impact of Turner syndrome at the moment of the diagnosis, their understanding of the syndrome, its effect in their lives, and their expectations for the future. RESULTS: Only 31% of the patients immediately understood the diagnosis. Their feelings associated to that moment were neutral (47%) or concerned (33%). About one third of the interviewed women were unable to explain the etiology of Turner syndrome (42%), did not relate their symptoms with Turner syndrome (36%), and/or believe there might be a cure for it (44%). Although most of the interviewed women affirm that the syndrome has no interference in their lives (67%) and that they consider themselves happy persons (78%), in more than half of the interviews there are evidences of difficulties in social interaction and love relationship, low self-esteem, dissatisfaction with their physical appearances, especially the short stature and infertility. Their hopes for the future refer mainly to study and have a job. Although being, on average, 19 years old, one in two women (53%) still hopes to grow up. CONCLUSION: Besides medical treatment, it is important that the knowledge of the patients about the syndrome and some issues as infertility, short stature, self-esteem and social interactions receive proper and continuous attention from the moment of the diagnosis. The ideal situation should be a joint-action of a psychologist and the medical team.OBJECTIVE To identify how patients with Turner syndrome perceive their condition. METHODS Thirty-six women with Turner syndrome, aged between 15 and 25 years and with over 2 years of medical follow-up, were individually interviewed about: the impact of Turner syndrome at the moment of the diagnosis, their understanding of the syndrome, its effect in their lives, and their expectations for the future. RESULTS Only 31% of the patients immediately understood the diagnosis. Their feelings associated to that moment were neutral (47%) or concerned (33%). About one third of the interviewed women were unable to explain the etiology of Turner syndrome (42%), did not relate their symptoms with Turner syndrome (36%), and/or believe there might be a cure for it (44%). Although most of the interviewed women affirm that the syndrome has no interference in their lives (67%) and that they consider themselves happy persons (78%), in more than half of the interviews there are evidences of difficulties in social interaction and love relationship, low self-esteem, dissatisfaction with their physical appearances, especially the short stature and infertility. Their hopes for the future refer mainly to study and have a job. Although being, on average, 19 years old, one in two women (53%) still hopes to grow up. CONCLUSION Besides medical treatment, it is important that the knowledge of the patients about the syndrome and some issues as infertility, short stature, self-esteem and social interactions receive proper and continuous attention from the moment of the diagnosis. The ideal situation should be a joint-action of a psychologist and the medical team.

RECURRENCE OF A NONSENSE MUTATION IN THE CONSERVED DOMAIN OF SRY IN A BRAZILIAN PATIENT WITH 46,XY GONADAL DYSGENESIS

We tested a female patient with 46,XY karyotype and pure gonadal dysgenesis for the presence of the SRY gene and for mutations within the SRY conserved domain. A point mutation was identified at nucleotide position 209 with respect to the first ATG. The base substitution is a G-->A transition in the first nucleotide of codon 70 which changes a tryptophan (TGG) to a stop codon (TAG). Even though the father was not available for investigation we assumed that it is a de novo mutation, since it probably generates a nonfunctional truncated protein.

Variables associated with diagnostic delay in Turner syndrome

Objective: To investigate the possible reasons for diagnostic delay in Turner syndrome (TS), i.e., a diagnosis made after the age when pubertal delay may be established. Methods: Cross-sectional study with data obtained from the records of 29 TS patients aged more than two years who were diagnosed between 2004 and 2007. Data on personal and family history and physical examination from patients diagnosed before 13 years old (age limit from which pubertal delay may be characterized in girls) were compared to those of girls diagnosed after 13 years by Fisher exact test and Student’s t-test. Results: No significant differences were noted regard ing mothers’ and patients’ stature, personal history of TS-associated diseases (considered individually), parental schooling, familial recurrence of short stature, presence of each dysmorphic feature considered separately, and total number of dysmorphic features. The two groups differed regarding the presence of at least one TS-associated disease (which was associated to early diagnosis) and number of siblings (which was higher among patients with delayed diagnosis and associated with lower maternal schooling). Conclusions: Early diagnosis was more associated with the presence of a TS-associated disease (which may have required referral to secondary or tertiary health care services) than with the presence of dysmorphic signs. The results indicate that less evident growth deficit, physicians’ inability to recognize abnormalities associated with TS and socioeconomic aspects may contribute to diagnostic delay. Pediatric training should emphasize recognition of the clinical spectrum of TS and public genetic services should be expanded.OBJETIVO: Investigar as possiveis razoes do atraso no diagnostico da sindrome de Turner (ST), ou seja, aquele realizado apos a idade em que se pode estabelecer o atraso puberal. METODOS: Estudo transversal com obtencao de dados dos prontuarios de 29 pacientes com ST diagnosticadas com mais de dois anos, entre 2004 e 2007. Foram comparados antecedentes pessoais e familiares e dados de exame fisico das pacientes diagnosticadas com menos de 13 anos (limite a partir do qual se pode caracterizar atraso puberal em meninas) com os daquelas diagnosticadas apos os 13 anos por meio dos testes t de Student e exato de Fisher. RESULTADOS: Nao houve diferencas significativas quanto a estatura materna e da propria paciente, historia de afeccoes associadas (consideradas individualmente), escolaridade dos pais, recorrencia familiar de baixa estatura, presenca de cada sinal dismorfico isoladamente e total de sinais observados. Os dois grupos diferiram quanto a presenca de ao menos uma afeccao sugestiva dessa sindrome (associada ao diagnostico mais precoce) e ao numero de irmaos (maior no diagnostico tardio e associado a menor escolaridade materna). CONCLUSOES: O diagnostico precoce relacionou-se mais a presenca de alguma das afeccoes associadas a ST (possivelmente determinando-se encaminhamento a servicos de maior complexidade) do que a sinais dismorficos. Ha indicacoes de que deficit de crescimento menos evidente, dificuldade dos medicos em reconhecer anomalias sugestivas dessa sindrome e determinantes socioeconomicos contribuam para o atraso no diagnostico. E necessario enfatizar na formacao pediatrica o reconhecimento do espectro clinico dessa sindrome e ampliar os servicos publicos de genetica.

Turner syndrome: the patients' view

OBJECTIVE: To identify how patients with Turner syndrome perceive their condition. METHODS: Thirty-six women with Turner syndrome, aged between 15 and 25 years and with over 2 years of medical follow-up, were individually interviewed about: the impact of Turner syndrome at the moment of the diagnosis, their understanding of the syndrome, its effect in their lives, and their expectations for the future. RESULTS: Only 31% of the patients immediately understood the diagnosis. Their feelings associated to that moment were neutral (47%) or concerned (33%). About one third of the interviewed women were unable to explain the etiology of Turner syndrome (42%), did not relate their symptoms with Turner syndrome (36%), and/or believe there might be a cure for it (44%). Although most of the interviewed women affirm that the syndrome has no interference in their lives (67%) and that they consider themselves happy persons (78%), in more than half of the interviews there are evidences of difficulties in social interaction and love relationship, low self-esteem, dissatisfaction with their physical appearances, especially the short stature and infertility. Their hopes for the future refer mainly to study and have a job. Although being, on average, 19 years old, one in two women (53%) still hopes to grow up. CONCLUSION: Besides medical treatment, it is important that the knowledge of the patients about the syndrome and some issues as infertility, short stature, self-esteem and social interactions receive proper and continuous attention from the moment of the diagnosis. The ideal situation should be a joint-action of a psychologist and the medical team.OBJECTIVE To identify how patients with Turner syndrome perceive their condition. METHODS Thirty-six women with Turner syndrome, aged between 15 and 25 years and with over 2 years of medical follow-up, were individually interviewed about: the impact of Turner syndrome at the moment of the diagnosis, their understanding of the syndrome, its effect in their lives, and their expectations for the future. RESULTS Only 31% of the patients immediately understood the diagnosis. Their feelings associated to that moment were neutral (47%) or concerned (33%). About one third of the interviewed women were unable to explain the etiology of Turner syndrome (42%), did not relate their symptoms with Turner syndrome (36%), and/or believe there might be a cure for it (44%). Although most of the interviewed women affirm that the syndrome has no interference in their lives (67%) and that they consider themselves happy persons (78%), in more than half of the interviews there are evidences of difficulties in social interaction and love relationship, low self-esteem, dissatisfaction with their physical appearances, especially the short stature and infertility. Their hopes for the future refer mainly to study and have a job. Although being, on average, 19 years old, one in two women (53%) still hopes to grow up. CONCLUSION Besides medical treatment, it is important that the knowledge of the patients about the syndrome and some issues as infertility, short stature, self-esteem and social interactions receive proper and continuous attention from the moment of the diagnosis. The ideal situation should be a joint-action of a psychologist and the medical team.

Fatores associados a atraso no diagnóstico da síndrome de Turner

Objective: To investigate the possible reasons for diagnostic delay in Turner syndrome (TS), i.e., a diagnosis made after the age when pubertal delay may be established. Methods: Cross-sectional study with data obtained from the records of 29 TS patients aged more than two years who were diagnosed between 2004 and 2007. Data on personal and family history and physical examination from patients diagnosed before 13 years old (age limit from which pubertal delay may be characterized in girls) were compared to those of girls diagnosed after 13 years by Fisher exact test and Student’s t-test. Results: No significant differences were noted regard ing mothers’ and patients’ stature, personal history of TS-associated diseases (considered individually), parental schooling, familial recurrence of short stature, presence of each dysmorphic feature considered separately, and total number of dysmorphic features. The two groups differed regarding the presence of at least one TS-associated disease (which was associated to early diagnosis) and number of siblings (which was higher among patients with delayed diagnosis and associated with lower maternal schooling). Conclusions: Early diagnosis was more associated with the presence of a TS-associated disease (which may have required referral to secondary or tertiary health care services) than with the presence of dysmorphic signs. The results indicate that less evident growth deficit, physicians’ inability to recognize abnormalities associated with TS and socioeconomic aspects may contribute to diagnostic delay. Pediatric training should emphasize recognition of the clinical spectrum of TS and public genetic services should be expanded.OBJETIVO: Investigar as possiveis razoes do atraso no diagnostico da sindrome de Turner (ST), ou seja, aquele realizado apos a idade em que se pode estabelecer o atraso puberal. METODOS: Estudo transversal com obtencao de dados dos prontuarios de 29 pacientes com ST diagnosticadas com mais de dois anos, entre 2004 e 2007. Foram comparados antecedentes pessoais e familiares e dados de exame fisico das pacientes diagnosticadas com menos de 13 anos (limite a partir do qual se pode caracterizar atraso puberal em meninas) com os daquelas diagnosticadas apos os 13 anos por meio dos testes t de Student e exato de Fisher. RESULTADOS: Nao houve diferencas significativas quanto a estatura materna e da propria paciente, historia de afeccoes associadas (consideradas individualmente), escolaridade dos pais, recorrencia familiar de baixa estatura, presenca de cada sinal dismorfico isoladamente e total de sinais observados. Os dois grupos diferiram quanto a presenca de ao menos uma afeccao sugestiva dessa sindrome (associada ao diagnostico mais precoce) e ao numero de irmaos (maior no diagnostico tardio e associado a menor escolaridade materna). CONCLUSOES: O diagnostico precoce relacionou-se mais a presenca de alguma das afeccoes associadas a ST (possivelmente determinando-se encaminhamento a servicos de maior complexidade) do que a sinais dismorficos. Ha indicacoes de que deficit de crescimento menos evidente, dificuldade dos medicos em reconhecer anomalias sugestivas dessa sindrome e determinantes socioeconomicos contribuam para o atraso no diagnostico. E necessario enfatizar na formacao pediatrica o reconhecimento do espectro clinico dessa sindrome e ampliar os servicos publicos de genetica.

Investigación de factores asociados a retraso en el diagnóstico del síndrome de Turner

Objective: To investigate the possible reasons for diagnostic delay in Turner syndrome (TS), i.e., a diagnosis made after the age when pubertal delay may be established. Methods: Cross-sectional study with data obtained from the records of 29 TS patients aged more than two years who were diagnosed between 2004 and 2007. Data on personal and family history and physical examination from patients diagnosed before 13 years old (age limit from which pubertal delay may be characterized in girls) were compared to those of girls diagnosed after 13 years by Fisher exact test and Student’s t-test. Results: No significant differences were noted regard ing mothers’ and patients’ stature, personal history of TS-associated diseases (considered individually), parental schooling, familial recurrence of short stature, presence of each dysmorphic feature considered separately, and total number of dysmorphic features. The two groups differed regarding the presence of at least one TS-associated disease (which was associated to early diagnosis) and number of siblings (which was higher among patients with delayed diagnosis and associated with lower maternal schooling). Conclusions: Early diagnosis was more associated with the presence of a TS-associated disease (which may have required referral to secondary or tertiary health care services) than with the presence of dysmorphic signs. The results indicate that less evident growth deficit, physicians’ inability to recognize abnormalities associated with TS and socioeconomic aspects may contribute to diagnostic delay. Pediatric training should emphasize recognition of the clinical spectrum of TS and public genetic services should be expanded.OBJETIVO: Investigar as possiveis razoes do atraso no diagnostico da sindrome de Turner (ST), ou seja, aquele realizado apos a idade em que se pode estabelecer o atraso puberal. METODOS: Estudo transversal com obtencao de dados dos prontuarios de 29 pacientes com ST diagnosticadas com mais de dois anos, entre 2004 e 2007. Foram comparados antecedentes pessoais e familiares e dados de exame fisico das pacientes diagnosticadas com menos de 13 anos (limite a partir do qual se pode caracterizar atraso puberal em meninas) com os daquelas diagnosticadas apos os 13 anos por meio dos testes t de Student e exato de Fisher. RESULTADOS: Nao houve diferencas significativas quanto a estatura materna e da propria paciente, historia de afeccoes associadas (consideradas individualmente), escolaridade dos pais, recorrencia familiar de baixa estatura, presenca de cada sinal dismorfico isoladamente e total de sinais observados. Os dois grupos diferiram quanto a presenca de ao menos uma afeccao sugestiva dessa sindrome (associada ao diagnostico mais precoce) e ao numero de irmaos (maior no diagnostico tardio e associado a menor escolaridade materna). CONCLUSOES: O diagnostico precoce relacionou-se mais a presenca de alguma das afeccoes associadas a ST (possivelmente determinando-se encaminhamento a servicos de maior complexidade) do que a sinais dismorficos. Ha indicacoes de que deficit de crescimento menos evidente, dificuldade dos medicos em reconhecer anomalias sugestivas dessa sindrome e determinantes socioeconomicos contribuam para o atraso no diagnostico. E necessario enfatizar na formacao pediatrica o reconhecimento do espectro clinico dessa sindrome e ampliar os servicos publicos de genetica.