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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1350-1356, 2019 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-31852638

RESUMO

OBJECTIVE: To investigate the feasibility of noninvasive prenatal genetic testing for detecting chromosome aneuploid in pregnant women aged less than 35 years with positive results in serum screening. METHODS: We analyzed the plasma cellfree fetal DNA in a total of 6804 pregnant women aged less than 35 years with singleton pregnancy from Foshan maternal and child health care hospital, whose weeks of gestation ranged from 12 to 24 weeks with ages on the expected date of confinement of 21-34 years. According to the results of serum screening, the women were divided to high-risk group and critical-risk group. Amniocentesis or cordocentesis was carried out if the results of noninvasive prenatal genetic testing were positive, and karyotyping or/and high-throughput sequencing was performed as the golden standard. All the women were followed up by telephone calls to assess the accuracy of the prenatal testing. RESULTS: Noninvasive prenatal testing was successfully completed in all the 6081 cases. In the high-risk group, 70 women with positive results were tested by noninvasive prenatal testing, among whom 53 were confirmed by karyotyping or high-throughput sequencing. In this group, the sensitivity, specificity and positive predictive value of trisomy 21 syndrome detection was 95.65%, 99.91% and 88.0%, respectively, with a false positive rate of 0.09% and a false negative rate of 4.35%; the sensitivity, specificity and positive predictive value for trisomy 18 syndrome was 100%, 100% and 100%, respectively, with false positive and false negative rates of 0; the false positive rate and false negative rate for trisomy 13 syndrome was 0.09% and 0, respectively; the sensitivity, specificity and positive predictive value for sex chromosome aneuploid as 100%, 99.80% and 30.0%, respectively, with a false positive rate of 0.2% and a false negative rate of 0; the sensitivity, specificity and positive predictive value for other chromosome aneuploid was 100%, 99.88% and 16.60%, respectively, with a false positive rate of 0.18% and a false negative rate of 0. In the critical risk group, 54 women with positive results received noninvasive prenatal genetic testing, among whom 36 were confirmed by karyotyping or high-throughput sequencing. The sensitivity, specificity and positive predictive value for trisomy 21 syndrome were all 100% and the false positive rate and false negative rate were both 0; the false positive rate was 0.11% and the false negative rate was 0 for trisomy 18 syndrome; the false positive rate and false negative rate for trisomy 13 syndrome was 0.04% and 0, respectively; the sensitivity, specificity and positive predictive value for sex chromosome aneuploid was 100%, 99.79% and 50.0%, respectively, with a false positive rate of 0.21% and a false negative rate of 0; the false positive rate for other chromosome aneuploid was 0.18% and the false negative rate was 0. No significant differences were found between the two groups in the sensitivity, specificity, positive predictive value and false positive rate for detection of trisomy 21 syndrome and sex chromosome aneuploid (P>0.05). CONCLUSIONS: Noninvasive prenatal genetic testing is necessary for high-risk pregnant women with critical-risk in serum screening who refuse invasive prenatal diagnosis, and it is highly sensitive and specific fir detecting chromosome aneuploid with low false positive and false negative rates.


Assuntos
Transtornos Cromossômicos , Diagnóstico Pré-Natal , Adulto , Cromossomos Humanos Par 18 , Feminino , Testes Genéticos , Humanos , Cariotipagem , Gravidez , Adulto Jovem
2.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(12): 881-887, 2019 Dec 07.
Artigo em Chinês | MEDLINE | ID: mdl-31887812

RESUMO

Objective: To screen, diagnose and follow up the abnormal mutation in the gene screening of neonatal deafness. Methods: A total of 24161 newborns born in Zhuhai Maternal and Child Health Hospital from February 1, 2015 to January 31, 2008 were screened for hearing and deafness genes, and audiological screening, diagnosis and 1-3 years follow-up were carried out for the newborns with positive gene screening. Results: There were 991 cases of deafness gene mutation (533 males and 458 females), and the rate of abnormal mutation was 4.10%(991/24 161). Among them, 921 cases were single heterozygous mutation, 130 cases were failed in primary hearing screening, 11 cases were failed in secondary hearing screening, 8 cases were abnormal in audiological diagnosis finally. In these 8 cases, 3 were diagnosed as otitis media and passed audiological follow-up after cure, 2 cases of single ear sensorineural injury caused by high-risk factors, passed after close audiological follow-up, and the other 3 cases were closely audiological follow-up while none of them were successfully sequenced. All of them were moderate to severe sensorineural deafness, 1 case was heterozygous mutation at 3 loci of GJB2(c.235delC,c.408C>A,c.134G>A), 1 case was heterozygous mutation at 2 loci of GJB2(c.235delC, c.109G>A), and 1 case was single heterozygous mutation of GJB2(c.235delC). The remaining 913 cases who passed the primary screening, secondary screening or hearing diagnosis were followed up for 1 to 3 years. Three cases of multiple heterozygous mutation were found in gene screening(2 cases were SLC26A4 2168A>G, IVS7-2A>G, 1 case was GJB2 c.176_191del 16bp, c.299_300del AT), all of them passed both primary and secondary hearing screening. In these 3 cases, the final audiological diagnosis was moderate sensorineural deafness in both ears, with no improvement in the follow-up of 1-3 years. There were 9 monogenic homozygous mutations, 7 failed in primary hearing screening, 3 failed in secondary hearing screening and also failed in audiological diagnosis and 1-3 years' audiological follow-up, all of whom were GJB2 c.235 del C homozygous mutations, and one of whom had a definite family history of deafness. The remaining 6 cases of homozygous mutation diagnosed by primary screening, secondary screening or hearing diagnosis were GJB2 c109G>A homozygous mutation, and passed the 1-3 years' hearing follow-up. 58 children with mtDNA mutations, including 2 with 12S rRNA 1494C>T homozygous mutation, 47 with 1555A>G homozygous mutation, and 9 with 1555A>G heterozygous mutation, all passed the primary or secondary hearing screening, and were instructed to ban ototoxic drugs for the whole life, and passed the 1-3 years' hearing follow-up. Conclusions: The audiological follow-up of children with monogenic heterozygous mutations in deafness gene screening is generally normal. In case of abnormality, the influencing factors such as otitis media should be excluded at first. In case of unexplained moderate to severe sensorineural deafness, the whole-gene sequencing should be performed to find possible pathogenic factors. The children with homozygous mutation or compound heterozygous mutation in gene screening, most of whom show different degrees of hearing loss, should be followed up for a long time, and provide parents with scientific and reasonable genetic counseling according to the mutation genes and loci,. The hearing of drug-induced deafness gene carriers is normal after birth. Parents should be advised to strengthen prevention and follow-up is generally enough.


Assuntos
Análise Mutacional de DNA , Surdez , Perda Auditiva , Pré-Escolar , China , Conexina 26 , Conexinas , Feminino , Seguimentos , Testes Genéticos , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Triagem Neonatal
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1085-1089, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703131

RESUMO

OBJECTIVE: To delineate the clinical and genetic features of two pedigrees affected with aromatic L-amino acid decarboxylase (AADC) deficiency. METHODS: The clinical features, family history and results of genetic testing of 2 patients with AADC deficiency were retrospectively analyzed. RESULTS: Both patients featured hypotension, developmental delay and oculogyric crisis during infancy. Genetic testing confirmed that they have respectively carried c.714+ 4 (IVS6) A to T/c.175(exon2)G TO A compound heterozygous variants and c.714+ 4(IVS6)A to T homozygous variant. CONCLUSION: The clinical manifestation of children with AADC deficiency may include hypotonia, developmental delay and paroxysmal oculogyric crisis. The combination of 3-O-methyldopa testing and variant analysis is not only very useful for early diagnosis, but also important for the evaluation of treatment effect and prognosis of the disease. Discovery of the novel variants has enriched the variant spectrum of AADC deficiency.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Descarboxilases de Aminoácido-L-Aromático/deficiência , Descarboxilases de Aminoácido-L-Aromático/genética , Testes Genéticos , Análise Mutacional de DNA , Humanos , Lactente , Linhagem , Estudos Retrospectivos
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1100-1103, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703135

RESUMO

OBJECTIVE: To analyze the phenotype and F5 gene variant in a pedigree affected with hereditary coagulation factor V (FV) deficiency. METHODS: All of the exons, flanking sequences, and 5' and 3' untranslated regions of the F5 gene were subjected to PCR and direct sequencing. Suspected variant sites were confirmed by clone sequencing. Influence of the variants was predicted by using software including ClustalX and Mutation Taster. RESULTS: The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were prolonged to 20.3 s and 59.2 s, respectively, while FV activity (FV:C) and FV antigen (FV:Ag) were reduced by 13% and 17%, respectively. The FV:C and FV:Ag of his father, sister and daughter were decreased to 35%, 37%, 29% and 42%, 46%, 35%, respectively. The proband was found to carry a heterozygous c.2851delT variant in exon 13 of the F5 gene, which caused a frameshift and resulted in a truncated protein (p.Ser923LeufsX8). In addition, a heterozygous c.1538G to A (p.Arg485Lys) variant was found in exon 10. The father, sister and daughter of the proband all carried the p.Ser923LeufsX8 variant, while his mother and son carried the heterozygous p.Arg485Lys polymorphism. His younger brother and wife were of the wild type. Bioinformatic analysis showed that p.Ser923 was highly conserved across various species. Mutation Taster scored 1.00 for the p.Ser923LeufsX8 variant, and the result has predicted a corresponding disease. CONCLUSION: A heterozygous deletional mutation c.2851delT in exon 13 of the F5 gene and a heterozygous c.1538G to A polymorphism harbored by the proband may be associated with the decreased FV level in this pedigree.


Assuntos
Deficiência do Fator V/genética , Fator V/genética , Deleção de Genes , Feminino , Testes Genéticos , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Fenótipo
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1104-1106, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703136

RESUMO

OBJECTIVE: To explore the genetic basis for a pedigree affected with X-linked adrenoleukodystrophy presenting as spastic paraplegia of the lower limbs. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his mother. Potential variant was detected with a panel for genes associated with spastic paraplegia. Candidate variant was verified by PCR and Sanger sequencing. RESULTS: Both the proband and his mother presented with walking difficulty. A previously known variant, c.623T to A (p.V208E), was identified in the ABCD1 gene mapped on chromosome X in both. CONCLUSION: X-link adrenoleukodystrophy should be taken into account as a possible diagnosis for this pedigree.


Assuntos
Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP/genética , Adrenoleucodistrofia/genética , Feminino , Testes Genéticos , Humanos , Masculino , Linhagem , Paraplegia Espástica Hereditária
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1115-1119, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703139

RESUMO

OBJECTIVE: To explore the genetic basis for a boy with mental retardation. METHODS: Clinical data and peripheral blood samples of the family were collected. Potential variants were screened by using a panel for genes associated with intellectual impairment. Suspected variants were verified by PCR and Sanger sequencing. RESULTS: The child presented with mental retardation, language delay and poor self-care. Imaging analysis showed widening of brain fissures and subarachnoid space, and dysplasia of corpus callosum. Three novel heterozygous variants, namely c.1705T to C (p.S569P), c.1708dupC (p.R570Pfs*80) and c.2273delA (p.N758Tfs*22), were identified in the TRAPPC9 gene. The mother of the proband has carried the c.1708dupC (p.R570Pfs*80) and c.1705T to C (p.S569P) variants, while his father has carried the c.2273delA (p.N758Tfs*22) variant. CONCLUSION: The compound heterozygous variants of the TRAPPC9 gene probably underlie the disease in this family. Considering the clinical and genetic heterogeneity of mental retardation, genetic testing is essential for attaining diagnosis for patients with the relevant phenotype.


Assuntos
Proteínas de Transporte/genética , Deficiência Intelectual/genética , Criança , Testes Genéticos , Heterozigoto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Mutação , Fenótipo
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1130-1132, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703143

RESUMO

OBJECTIVE: To analyze the hematological characteristics of a patient with Hb Ottawa in conjunction with ß -thalassemia. METHODS: Peripheral blood samples from the proband and her parents were collected and subjected to red blood cell analysis and hemoglobin electrophoresis. Genotypes of α - and ß -globin genes were also analyzed. RESULTS: The proband and her mother were both heterozygotes for Hb Ottawa and ß -thalassemia variant IVS II-654, and presented with typical ß -thalassemia trait featuring hypochromic microcytic anemia. An abnormal hemoglobin band was detected upon electrophoresis. CONCLUSION: Co-existence of Hb Ottawa and ß -thalassemia may not aggravate the phenotype.


Assuntos
Hemoglobinas Anormais/genética , Talassemia beta/genética , Feminino , Testes Genéticos , Heterozigoto , Humanos , alfa-Globinas/genética , Globinas beta/genética
9.
Zhonghua Yan Ke Za Zhi ; 55(11): 806-810, 2019 Nov 11.
Artigo em Chinês | MEDLINE | ID: mdl-31715676

RESUMO

Retinoblastoma, the most frequent malignant intraocular tumor in childhood, is caused by oncogenic mutations in the RB1 tumor suppressor gene. Identification of these mutations in patients is important for genetic counseling and clinical management of relatives at risk, and thus probands are conventionally applied gene detection in developed countries. However, gene diagnosis is still in the elementary period in China. This article reviews the characteristics of retinoblastoma genetics and the current status of genetic testing in China, so as to attract more attention from ophthalmologists and to promote regulated gene diagnosis in clinical work. Not only does good understanding of retinoblastoma genetics support optimal care for retinoblastoma children and their families, but also promotes the development in foundational research. (Chin J Ophthalmol, 2019, 55: 806-810).


Assuntos
Testes Genéticos , Neoplasias da Retina/diagnóstico , Retinoblastoma/diagnóstico , Criança , China , Análise Mutacional de DNA , Genes do Retinoblastoma , Humanos , Mutação , Neoplasias da Retina/genética , Retinoblastoma/genética , Proteínas de Ligação a Retinoblastoma/genética , Ubiquitina-Proteína Ligases/genética
10.
Gan To Kagaku Ryoho ; 46(11): 1761-1764, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31748488

RESUMO

Herein, we report the manifestation of type 1A Charcot-Marie-Tooth disease(CMT)in a 54-year-old female gastric cancer patient caused by oxaliplatin(L-OHP)of neoadjuvant chemotherapy containing S-1 plus L-OHP(G-SOX). In this case, peripheral sensory neuropathy(PSN)appeared in both upper limbs immediately after the administration of L-OHP. Subsequently, we observed sensory neuropathy of gloves-socks type in both the upper and lower limbs and motor neuropathy in both lower limbs, which caused the patient to be unable to sit up. Physical examination revealed upside-down champagnebottle- like mild atrophy in both lower limbs and hollow feet in both legs, as well as the disappearance of deep tendon reflexes in both lower limbs. In her family history, her eldest daughter had undergone Achilles tendon elongation surgery for suspected CMT at the age of 3 years. Considering these, she was suspected to have CMT and was finally diagnosed with type 1A CMT based on genetic testing. In anti-cancer treatments that cause PSN(not just by L-OHP), possible involvement of occult peripheral nerve disease like CMT should be considered when more rapid and untypical PSN appears after the administration of anti-cancer drugs.


Assuntos
Doença de Charcot-Marie-Tooth , Neoplasias Gástricas/terapia , Feminino , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Oxaliplatina
11.
J Law Med ; 27(1): 108-121, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31682345

RESUMO

Disclosure of genetic information without consent of the patient (proband) challenges the legal frameworks of privacy and confidentiality. Changes to privacy legislation enable and provide guidelines for undertaking disclosure, with the purpose of reducing the harm to genetic relatives who, armed with such information, may seek predictive testing themselves. Nevertheless, significant uncertainty remains for health care professionals in the application of the discretion to disclose genetic information to at-risk relatives. First, jurisdictional inconsistencies in privacy legislation present challenges for the provision of genetic services across the country. Second, the current guidelines provide insufficient clarity regarding the justification for disclosure of genetic information to reduce psychological harm to relatives. Third, the implications of a potential expansion of a legal duty of care to inform genetic relatives in some circumstances indicates that such a duty would be unduly burdensome for health care professionals, and suggests that revision of the threshold for use - rather than disclosure - of depersonalised genetic information may represent a pragmatic way forward.


Assuntos
Revelação , Privacidade Genética , Austrália , Confidencialidade , Testes Genéticos , Humanos , Consentimento Livre e Esclarecido
12.
Rev Med Liege ; 74(11): 580-585, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31729846

RESUMO

The incidental finding of renal cysts is a common clinical situation given their high prevalence (~ 50 % after the age of 50) and the continuous improvement of abdomen imaging. Diagnosis is central to appropriately dictate the management of the patient. During the diagnostic work-up, it is important to consider (i) the aspect of the cysts, (ii) their number, (iii) and their location, as well as (iv) the age of the patient and his/her personal and familial medical history, (v) the presence of extra-renal manifestations, (vi) and the renal function (including the urinary sediment). Starting from an atypical clinical case characterized by a rapidly evolving chronic kidney disease associated with bilateral renal cysts, we review the classical diagnostic work-up of kidney cysts. As a conclusion, we propose a diagnostic algorithm including both acquired and hereditary nephropathies.


Assuntos
Cistos , Nefropatias/diagnóstico , Cistos/diagnóstico , Cistos/genética , Diagnóstico Diferencial , Feminino , Testes Genéticos , Humanos , Nefropatias/genética , Masculino
14.
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
15.
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
16.
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
17.
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
18.
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
19.
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
20.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(10): 764-768, 2019 Oct 07.
Artigo em Chinês | MEDLINE | ID: mdl-31606990

RESUMO

Objective: To study the diagnostic value of a multi-gene molecular testing in cytologically indeterminate thyroid nodules. Methods: From February 2018 to September 2018, patients with thyroid nodules who underwent fine needle aspiration(FNA) at Peking University Cancer Hospital were enrolled. Three hundred and sixty patients were included, consisting of 86 men and 274 women, with a mean age of 45.8 years (between 13 and 89 years old). Among 391 nodules, 141 were cytologically inderminate and 75 were resected. FNA samples underwent prospective testing using a next-generation sequencing (NGS) assay, which included 16 genes for point mutations and 26 types of gene fusions. The testing results of indeterminate nodules were compared with surgical outcomes, to determine the diagnostic performance. The results were compared with the BRAF V600E single gene mutation analysis by χ(2) test. Results: The multi-gene testing showed a sensitivity of 73.2%, specificity of 96.8%, positive predictive value of 96.8%, and negative predictive value of 73.2%. The diagnostic accuracy of multi-gene testing was significantly higher than the BRAF V600E mutation test (83.3% vs 73.6%, χ(2)=31.588, P<0.01). Conclusion: Multi-gene testing in FNA samples is an effective method to diagnose cytologically indeterminate thyroid nodules, which has a higher accuracy than BRAF V600E mutation detection.


Assuntos
Biópsia por Agulha Fina , Testes Genéticos , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Análise de Sequência , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/cirurgia , Adulto Jovem
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