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1.
Med Clin North Am ; 103(6): 1005-1019, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582001

RESUMO

Heritable thoracic aortic disease (HTAD) can have life-threatening consequences if not diagnosed early. Affected individuals and at-risk family members benefit from both cardiology and genetic evaluations, including genetic testing. Important information can be obtained through family history, medical history, and genetic testing to help guide management and assess risk. A genetic diagnosis can guide cardiovascular management (type and frequency of vascular imaging, timing of surgical intervention), risk assessment for arterial aneurysm/dissection, evaluation of nonvascular features, and familial testing.


Assuntos
Aorta Torácica/anormalidades , Doenças da Aorta , Testes Genéticos/métodos , Administração dos Cuidados ao Paciente/métodos , Doenças da Aorta/genética , Doenças da Aorta/terapia , Humanos , Medicina de Precisão/métodos
2.
Med Clin North Am ; 103(6): 1035-1054, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582003

RESUMO

Neurofibromatosis type 1 (NF1), NF2, and schwannomatosis are related, but distinct, tumor suppressor syndromes characterized by a predilection for tumors in the central and peripheral nervous systems. NF1 is one of the most common autosomal dominant conditions of the nervous system. NF1 has a high degree of variability in clinical presentation, which may include multiple neoplasms as well as cutaneous, vascular, bony, and cognitive features. Some of these manifestations overlap with other genetic conditions. Accurate diagnosis of NF1 is important for individualizing clinical care and genetic counseling. This article summarizes the clinical features, diagnostic work-up, and management of NF1.


Assuntos
Testes Genéticos/métodos , Neurilemoma/diagnóstico , Neurofibromatoses/diagnóstico , Neurofibromatose 1 , Neoplasias Cutâneas/diagnóstico , Diagnóstico Diferencial , Gerenciamento Clínico , Humanos , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/terapia
3.
Med Clin North Am ; 103(6): 1055-1075, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582004

RESUMO

This article presents a nongeneticist's guide to understanding the genetics of Parkinson disease (PD), including clinical diagnostic criteria, differential diagnoses, symptom management, when to suspect a hereditary factor, a summary of autosomal dominant and recessive PD genes, and proposed algorithm for genetic testing. There is increasing availability of genetic testing for PD but there are few recommendations on how these tests should be used in clinical practice. This article guides clinicians on the overall management of patients with PD, with emphasis on determining which patients should have genetic testing and how to interpret the results.


Assuntos
Testes Genéticos/métodos , Doença de Parkinson , Algoritmos , Gerenciamento Clínico , Predisposição Genética para Doença , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Doença de Parkinson/terapia
4.
Med Clin North Am ; 103(6): 1077-1092, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582005

RESUMO

Compared to clinicians previously surveyed, primary care providers employed in a health system known for clinical genomics were more likely to have ordered or referred a patient for genetic testing, but had only modestly more genetics training and reported similarly low levels of comfort answering patient questions about genetic risk. Most supported population genomic screening, reported willingness to get screened themselves, and judged a hypothetical patient's decision to be screened favorably relative to a similar patient's decision to decline screening. Stakeholder perceptions of the ethical appropriateness of nudging at-risk patients to discuss testing with counselors were mixed.


Assuntos
Aconselhamento Genético , Testes Genéticos/métodos , Atenção Primária à Saúde , Aconselhamento Genético/ética , Aconselhamento Genético/métodos , Aconselhamento Genético/psicologia , Humanos , Medicina de Precisão/métodos , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/tendências , Sequenciamento Completo do Exoma
5.
Med Clin North Am ; 103(6): 957-966, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582006

RESUMO

The collection of family history has always been a tool for genetic evaluation, but it remains an essential tool even in the age of genomic medicine. Patients may have a risk for a disease based on family history regardless of the results of genetic and genomic tests. How this information is collected is less important than that relevant information is collected in the first place. There are many tools for collecting medical and family history information both by hand and electronically. Genetic and genomic testing should always be interpreted in the context of the personal and family history.


Assuntos
Testes Genéticos/métodos , Anamnese/métodos , Medicina de Precisão , Humanos , Linhagem , Medição de Risco
6.
Med Clin North Am ; 103(6): 991-1003, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582009

RESUMO

Genetic causes of liver disease lead to a wide range of presentations. This article describes hereditary hemochromatosis, Gilbert syndrome, alpha-1 antitrypsin deficiency, Wilson disease, PFIC, BRIC, and LAL-D. The most common cause of hereditary hemochromatosis is a C282Y mutation in the HFE gene. Gilbert syndrome is a benign cause of indirect hyperbilirubinemia. Alpha-1 antitrypsin deficiency causes both lung and liver disease. Wilson disease can cause neurologic disease and liver disease. Progressive familial intrahepatic cholestasis and benign recurrent intrahepatic cholestasis are rare causes of cholestasis. LAL-D is a rare disease that can appear similar to NAFLD in adults.


Assuntos
Testes Genéticos , Hepatopatias , Administração dos Cuidados ao Paciente/métodos , Humanos , Hepatopatias/genética , Hepatopatias/terapia
7.
Medicine (Baltimore) ; 98(39): e17305, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574858

RESUMO

Until now, the recognition of sodium taurocholate cotransporting polypeptide (NTCP) deficiency has been mainly based on sporadic case reports. It was previously believed to be mildly symptomatic and resulting in mild liver dysfunction. However, to our knowledge, there have been no reports about the histopathologic and ultrastructural pathologic characteristics of the disease. The aim of the study was to analyze the clinical, histopathologic and ultrastructural pathologic characteristics of NTCP deficiency in 13 pediatric patients.From August 2012 to October 2018, this retrospective study conducted in the Department of Pediatrics of Tongji Hospital, China analyzed the data of 13 NTCP deficient patients with an SLC10A1 gene mutation. Except for NTCP deficiency, no other liver diseases were present in the patients, which was determined by both a genetic testing panel for jaundice and by reviewing medical records. The laboratory results, imaging, histopathologic, and ultrastructural pathologic information were recorded for analysis.The serum level of total bile acid was high in all 13 patients. All patients had adequate growth and development. Eight of the patients (8/13) presented with visible jaundice and 12 (12/13) were found to have hyperbilirubinemia. A needle liver biopsy was performed in 11 cases, which revealed slightly chronic inflammation in all 11 patients. One of the patients (1/13) was found to be suffering from gallstones.The data showed that although NTCP deficiency was often asymptomatic, some of the patients showed obvious clinical expressions, such as jaundice. Among the 13 pediatric patients with NTCP deficiency, both the biochemical and histopathologic features were similar to those of mild hepatocellular jaundice. In addition, it was determined that the clinical features in the patient with gallstones may have been caused by NTCP deficiency.


Assuntos
Ácidos e Sais Biliares/sangue , Icterícia , Hepatopatias , Fígado , Transportadores de Ânions Orgânicos Dependentes de Sódio , Simportadores , Desenvolvimento Infantil , Pré-Escolar , China/epidemiologia , Testes Genéticos/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Lactente , Icterícia/diagnóstico , Icterícia/etiologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias/diagnóstico , Hepatopatias/genética , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Testes de Função Hepática/métodos , Glicoproteínas de Membrana/metabolismo , Mutação , Transportadores de Ânions Orgânicos Dependentes de Sódio/deficiência , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Pediatria/métodos , Estudos Retrospectivos , Simportadores/deficiência , Simportadores/genética
8.
Brain Nerve ; 71(10): 1071-1079, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588051

RESUMO

Next generation sequencing (NGS) technology has dramatically influenced the field of omics studies, such as genomics and transcriptomics. It is now possible to access a significant number of previously known and novel genomic variants through NGS. Although the effective manipulation and accurate interpretation of the inordinate amount of data may pose a considerable challenge, it enables us to identify specific genes responsible for causing or influencing the susceptibility to a plethora of diseases. Alzheimer's disease (AD) is the most common etiology of dementia in the elderly (approximately 60-70%). The current research trend of AD genetics focuses on the analysis of rare variants (allelic frequency <1%) instead of common variants (allelic frequency >1%) to identify AD-associated genes/variants. A number of genes (such as TREM2, ABCA7, SORL1) that carry rare pathogenic variants have reportedly conferred susceptibility to AD with stronger genetic risk effects (odds ratio >2.0). Here, we are going to introduce a small part of the latest many attractive findings about AD genetic researches.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Transportadores de Cassetes de Ligação de ATP/genética , Alelos , Frequência do Gene , Testes Genéticos , Genômica , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Receptores Imunológicos/genética
9.
Brain Nerve ; 71(10): 1081-1088, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588052

RESUMO

During the past 20 years, genome studies for Alzheimer's disease (AD) have elucidated the pathogenesis of AD including the amyloid hypothesis. However, clinical trials of the disease modifying drugs for AD developed based on the amyloid hypothesis have been largely unsuccessful. New genes associated with AD have been identified through comprehensive genome analyses such as genome-wide association studies and whole genome/exome sequencing using next-generation sequencers. With these efforts, new therapeutic targets to AD have been explored. This review summarizes the genetic make-up of AD in terms of both risk and protective factors from the viewpoint of novel therapeutic targets to AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Testes Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Fatores de Proteção , Fatores de Risco
10.
Exp Suppl ; 111: 29-32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588526

RESUMO

In this brief chapter, clinically very important topics of family screening and genetic counseling are discussed that are also pivotal in endocrine genetics. Genetic screening makes possible to diagnose a genetic disease at an early stage or to exclude its presence. Family members have to be screened if a heritable disease is diagnosed. Personal consultation with the patient and the relatives is inevitable in every genetically determined disease. The main function of genetic counseling is the transfer of important pieces of information to the patient about the congenital or later-manifesting diseases. This process via the informed consent should give enough information to the patient and the relatives to make decisions about the disease. Genetic data should be considered as special data; therefore the protection of the personal data and the confidentiality obligation should be prevailed intensively. The chief goal of the genetic counseling is the prevention of the conception or the birth of a person who would suffer from a severe genetic disease and/or to present information of the chance for having an affected descendant. If the prevention is not feasible, the alternative aim is to prevent the development of the consequences or to moderate its severity. Genetic counseling has important ethical aspects such as prenatal genetic investigations; hereditary, but treatable, nonlethal diseases; and genetic diseases that manifest late, predominantly in the adulthood.


Assuntos
Saúde da Família , Aconselhamento Genético , Testes Genéticos , Confidencialidade , Humanos , Consentimento Livre e Esclarecido
11.
Exp Suppl ; 111: 33-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588527

RESUMO

Molecular genetic methods have become an organic part of everyday clinical practice. In the past, molecular diagnostic tests were carried out for genetic diagnosis of a particular monogenic disease. In these situations the tests itself were used for identification of one particular genetic alteration (e.g., point mutation or deletion) of the gene of interest. Later, parallel with the development of the technology, the focus has shifted by allowing investigating at once targeted gene panels and even the whole exome/genome behind a suspected genetic disorder. Historically for these purposes, array-based methods (oligonucleotide arrays) and then next-generation sequencing-based methods have been used. High-throughput methods have been fundamentally transforming the everyday, routine genetic diagnostics, but older molecular techniques still have a role in clinical genetics. Here, we summarize the most important molecular genetic methods and shed light to the advantages and disadvantages of their application in routine diagnostics. We mainly focus on methods used for detection of germline alterations.


Assuntos
Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Técnicas de Diagnóstico Molecular , Reação em Cadeia da Polimerase em Tempo Real , Exoma , Humanos , Mutação
12.
Exp Suppl ; 111: 341-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588539

RESUMO

Male infertility is a multifactorial and heterogeneous pathological condition affecting 7% of the general male population. The genetic landscape of male infertility is highly complex as semen and testis histological phenotypes are extremely heterogeneous, and at least 2000 genes are predicted to be involved in spermatogenesis. Genetic factors have been described in each etiological category of male reproductive impairment: (1) hypothalamic-pituitary axis dysfunction; (2) quantitative and qualitative alterations of spermatogenesis; (3) ductal obstruction/dysfunction. In 25% of azoospermic and in 10% of oligozoospermic men, a genetic anomaly can be diagnosed with the current genetic testing. However, up to now, only a relatively low number of monogenic factors have a clear-cut cause-effect relationship with impaired reproductive function. Thanks to the widespread diffusion of Next-Generation Sequencing, a continuously increasing number of monogenic causes of male infertility are being discovered and their validation is currently ongoing. The identification of genetic factors is of outmost clinical importance since there is a risk of transmission of genetic defects through natural or assisted reproductive techniques. The benefit of the genetic diagnosis of infertility has an obvious clinical significance for the patient itself with implications not only for his reproductive health but in many instances also for his general health.


Assuntos
Infertilidade Masculina/genética , Espermatogênese/genética , Testes Genéticos , Humanos , Masculino
13.
Exp Suppl ; 111: 385-416, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588541

RESUMO

In addition to the common types of diabetes mellitus, two major monogenic diabetes forms exist. Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic, autosomal dominant diseases. MODY accounts for 1-2% of all diabetes cases, and it is not just underdiagnosed but often misdiagnosed to type 1 or type 2 diabetes. More than a dozen MODY genes have been identified to date, and their molecular classification is of great importance in the correct treatment decision and in the judgment of the prognosis. The most prevalent subtypes are HNF1A, GCK, and HNF4A. Genetic testing for MODY has changed recently due to the technological advancements, as contrary to the sequential testing performed in the past, nowadays all MODY genes can be tested simultaneously by next-generation sequencing. The other major group of monogenic diabetes is neonatal diabetes mellitus which can be transient or permanent, and often the diabetes is a part of a syndrome. It is a severe monogenic disease appearing in the first 6 months of life. The hyperglycemia usually requires insulin. There are two forms, permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). In TNDM, the diabetes usually reverts within several months but might relapse later in life. The incidence of NDM is 1:100,000-1:400,000 live births, and PNDM accounts for half of the cases. Most commonly, neonatal diabetes is caused by mutations in KCNJ11 and ABCC8 genes encoding the ATP-dependent potassium channel of the ß cell. Neonatal diabetes has experienced a quick and successful transition into the clinical practice since the discovery of the molecular background. In case of both genetic diabetes groups, recent guidelines recommend genetic testing.


Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus/genética , Doenças do Recém-Nascido/genética , Testes Genéticos , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/genética , Humanos , Recém-Nascido , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genética , Proteínas Serina-Treonina Quinases/genética , Receptores Sulfonilureia/genética
14.
An Acad Bras Cienc ; 91(3): e20180882, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553368

RESUMO

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by dynamic mutations of a CGG repetition segment in an X chromosome's single gene. It is considered the leading hereditary cause of both Autism Spectrum Disorders and Intellectual Disability. Some authors suggest that all individuals diagnosed with some of these latter conditions to be clinically and molecularly trialled for FXS due to the high levels of comorbidity between both conditions and also due to the variable expressiveness of this syndrome. This study has focused on verifying the presence of FMR1 expanded alleles since there is a lack of information about this kind of mutation in autism patients from the northern region of Brazil. The presence of large alleles for this gene could offer new therapeutic or pharmacological methods for the treatment of these patients. Both the presence and the frequency of CGG expansions were verified in 90 autism males by molecular analysis. Four of them had intermediate alleles and four others presented premutated alleles. Premutation carriers are on the propensity of developing the late onset Fragile X-associated tremor/ataxia syndrome. No full mutation alleles were found. Further studies are necessary to obtain more accurate statistical data about this kind of dynamic mutation.


Assuntos
Transtorno do Espectro Autista/genética , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/genética , Mutação/genética , Adolescente , Alelos , Criança , Pré-Escolar , Predisposição Genética para Doença , Testes Genéticos , Humanos , Masculino , Adulto Jovem
15.
Phys Chem Chem Phys ; 21(37): 20678-20692, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31508628

RESUMO

In this work we present a high-throughput approach to the computation of absorption UV-Vis spectra tailored to mutagenesis studies. The scheme makes use of a single molecular dynamics trajectory of a reference (non-mutated) species. The shifts in absorption energy caused by a residue mutation are evaluated by building an effective potential of the environment and computing a correction term based on perturbation theory. The sampling is only performed in the phase space of the initial protein. We analyze the robustness of the method by comparing different approximations for the effective potential, the sampling of mutant residue geometries and observing the impact in the prediction of both bathocromic and hypsochromic shifts. As a test subject, we consider a red fluorescent protein variant with potential biotechnological applications.


Assuntos
Testes Genéticos/métodos , Luz , Proteínas/química , Proteínas/genética , Análise Espectral , Raios Ultravioleta , Simulação de Dinâmica Molecular , Mutação
16.
Zhonghua Er Ke Za Zhi ; 57(9): 674-679, 2019 Sep 02.
Artigo em Chinês | MEDLINE | ID: mdl-31530352

RESUMO

Objective: To examine genetic variants of familial hematuria (FH) associated genes in 3 families with hematuria with probands initially diagnosed with IgA nephropathy (IgAN). Methods: A retrospective analysis was performed on the clinical data, laboratory tests and genetic test results of three children with hematuria and the probands in three families with hematuria. The families were ascertained at the Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command from August 2014 to May 2018. Results: The proband of Family One, an 8-year-old boy, manifested gross hematuria. His renal biopsy pathology revealed IgAN. His father also manifested hematuria. Genetic testing showed that the proband and his father carried a heterozygous variant of the CFHR5 gene,533A>G (Asn178Ser). The child of Family Two, a 4-year-old girl, manifested hematuria. Her father, the proband of the family, was 36 years old, and manifested hematuria, proteinuria, high-frequency sensorineural deafness and renal insufficiency. He was diagnosed as IgAN according to clinical manifestations, renal pathology and routine immunohistochemistry without renal biopsy electron microscopy, renal tissue type Ⅳ collagen α3, α4, α5 chains immunofluorescence and skin type Ⅳ collagen α5 chain immunofluorescence. Genetic testing showed that the girl carried a heterozygous variant of the COL4A5 gene,566G>T (Gly189Val), and her father carried the hemizygous variant. The child of Family Three, a 7-year-old girl, manifested hematuria and proteinuria. Her mother, the proband of the family, was 34 years old, and manifested hematuria and proteinuria as well. The proband was diagnosed as IgAN by the same method used for Family Two. The girl's grandfather died of uremia at the age of 44. Genetic testing showed that the girl and her mother carried a heterozygous variant 539G>A (Gly180Glu)in COL4A5 gene. Conclusions: The variant of the CFHR5 gene identified in Family One is of uncertain signifance, and the two variants of the COL4A5 gene identified in Families Two and Three are pathogenic. The probands of Families Two and Three are diagnosed as Alport syndrome. The study suggests that clinicians should examine genetic variants of FH associated genes in families with hematuria when the probands were diagnosed as IgAN by their clinical manifestations, renal pathology and routine immunohistochemistry.


Assuntos
Variação Genética/genética , Hematúria/diagnóstico , Nefrite Hereditária/diagnóstico , Adulto , Criança , Pré-Escolar , Feminino , Testes Genéticos/métodos , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/patologia , Hematúria/genética , Humanos , Rim , Masculino , Nefrite Hereditária/genética , Estudos Retrospectivos , Sequenciamento Completo do Exoma
17.
Zhonghua Er Ke Za Zhi ; 57(9): 700-704, 2019 Sep 02.
Artigo em Chinês | MEDLINE | ID: mdl-31530356

RESUMO

Objective: To analyze and summarize the diagnosis and treatment experience of common inherited cardiac arrhythmia syndrome in pediatric patients, and explore the most appropriate therapy. Methods: A retrospective review identified 30 pediatric cases (19 males, 11 females) diagnosed with long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), hypertrophic cardiomyopathy (HCM), arrhythmogenc right ventricular cardiomyopathy (ARVC) from January 2008 to December 2018 in the Pediatric Cardiology Department, Guangdong Provincial People's Hospital. Data obtained included the diagnosis, treatment and follow-up outcome. Results: The most common inherited cardiac arrhythmia syndromes were LQTS (n=14) including 1 case with epilepsy, CPVT (n=5), HCM (n=7), ARVC (n=1), and BrS (n=3). Twenty-seven cases were admitted to hospital due to syncope, whereas the remaining 3 cases of BrS had not presented with syncope before admission. The average onset age of inherited arrhythmia was (10.0±3.3) years. Genetic testing was performed on 20 patients. The median follow-up time was 40 months. Among 15 patients who underwent implantable cardioverter defibrillator (ICD) and survived, 2 patients had frequent ICD discharge. One patient underwent radiofrequency ablation, and the other one received left cardiac sympathetic denervation and an increased ICD defibrillation threshold, and the number of ICD discharge was significantly reduced. Among 10 patients who received drug therapy, 4 patients including two patients who discontinued treatment without advices died. Two patients whose parents refused treatment died, 1 case diagnosed with unexplained sudden cerebral death, and the remaining 2 cases without indication for drug therapy survived without any treatment. Conclusions: Mortality rate is high in pediatric patients with inherited cardiac arrhythmia and syncope. The therapeutic effect of drugs are not satisfactory, ICD implantation is the most effective treatment to prevent sudden cardiac death currently, but the postoperative frequent discharge should be brought to the forefront and handled in time.


Assuntos
Displasia Arritmogênica Ventricular Direita/genética , Síndrome de Brugada/genética , Cardiomiopatia Hipertrófica/genética , Síndrome do QT Longo/genética , Taquicardia Ventricular/genética , Arritmias Cardíacas , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/mortalidade , Displasia Arritmogênica Ventricular Direita/terapia , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/mortalidade , Síndrome de Brugada/terapia , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/terapia , Criança , Morte Súbita Cardíaca , Desfibriladores Implantáveis , Feminino , Seguimentos , Testes Genéticos , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/mortalidade , Síndrome do QT Longo/terapia , Masculino , Estudos Retrospectivos , Síncope , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/terapia , Resultado do Tratamento
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 886-889, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515782

RESUMO

OBJECTIVE: To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS). METHODS: Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c.3779+1G>A and c.5052_c.5053insT, were respectively identified in the 2 patients. Among these, c.3779+1G>A was a previously known pathological mutation, while c.5052_c.5053insT was unreported previously. Both variants were predicted to be pathological. CONCLUSION: Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.


Assuntos
Proteína de Ligação a CREB/genética , Síndrome de Rubinstein-Taybi/genética , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fenótipo
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 890-892, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515783

RESUMO

OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with congenital limb malformations. METHODS: Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing. RESULTS: Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members. CONCLUSION: The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.


Assuntos
Deformidades Congênitas da Mão/genética , Deformidades Congênitas dos Membros/genética , Proteínas de Membrana/genética , Polidactilia/genética , Feminino , Testes Genéticos , Humanos , Masculino , Linhagem , Polegar/patologia
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 893-896, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515784

RESUMO

OBJECTIVE: To analyze genetic variant in a pedigree affected with congenital high myopia. METHODS: Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing. The pedigree was also subjected to co-segregation analysis. RESULTS: WES has identified a novel splice site heterozygous variant (c.2556+1G>A) in the COL11A1 gene in the proband. Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556+1G>A), while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants, the variant was classified as "likely pathogenic" (PVS1+PM2). CONCLUSION: A novel splice variant (c.2556+1G>A) of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia, which probably underlies the disease.


Assuntos
Colágeno Tipo XI/genética , Miopia/genética , Testes Genéticos , Heterozigoto , Humanos , Linhagem , Sequenciamento Completo do Exoma
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