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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 853-856, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487529

RESUMO

OBJECTIVE: To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS). METHODS: 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019. RESULTS: SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation. CONCLUSION: Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.


Assuntos
Síndrome da Deleção 22q11/diagnóstico por imagem , Diagnóstico Pré-Natal , Ultrassom , Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Feminino , Feto , Testes Genéticos , Humanos , Gravidez
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 865-868, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487532

RESUMO

OBJECTIVE: To analyze the clinical characteristics and genetic variants in a two-month-and-one-day male infant with aldosterone synthase deficiency. METHODS: Clinical data of the child was collected. Whole exome sequencing was carried out by next generation sequencing(NGS). Candidate variants were verified by Sanger sequencing. RESULTS: The infant had measured 54 cm (-2.1 SD) in length and 3.9 kg (-2.8 SD) in weight, and featured recurrent vomiting, poor feeding, apathetic appearance and failure to thrive. Blood electrolyte testing showed low sodium and increased potassium. Serum cortisol, adrenocorticotrophic hormone, 17-alpha-hydroxyl progesterone, androstenedione, and testosterone were all within the normal ranges. The plasma renin activity activity was increased, and plasma aldosterone level was low. NGS revealed that the infant has harbored compound heterozygous variants of the CYP11B2 gene, namely c.1334T>G(p.Phe445Cys) inherited from his father and c.1121G>A(p.Arg374Gln) inherited from his mother. Neither variant was reported previously, and both were predicted to be deleterious for the function of the protein product. CONCLUSION: The compound heterozygous variants of c.1334T>G (p.Phe445Cys) and c.1121G>A (p.Arg374Gln) of the CYP11B2 gene probably underlay the disease in this patient.


Assuntos
Citocromo P-450 CYP11B2 , Testes Genéticos , Criança , Citocromo P-450 CYP11B2/deficiência , Citocromo P-450 CYP11B2/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Mutação , Sequenciamento Completo do Exoma
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 873-876, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487534

RESUMO

OBJECTIVE: To report the clinical manifestation and genetic characteristics of a child with Thiamine metabolism dysfunction syndrome 5. METHODS: Clinical data and genetic results were collected and analyzed. Peripheral blood samples of the child and their parents were collected for whole exome sequencing, and the functional effect of the variants on the TPK1 enzyme activity was verified by an in vitro assay. RESULTS: A four-year-old boy presented with preschool onset of ataxia were characterized. High-throughput sequencing identified a novel homozygous variant of TPK1 gene c.382G>A (p.Leu128Phe). His father and mother were both found carrying the variant. The variant protein showed a 30.9% reduction in TPK1 enzyme activity compared with the wildtype. CONCLUSION: A novel pathogenic variant has been identified in a boy with thiamine metabolic dysfunction syndrome type 5.


Assuntos
Testes Genéticos , Tiamina , Pré-Escolar , Homozigoto , Humanos , Masculino , Mutação , Sequenciamento Completo do Exoma
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 845-848, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487527

RESUMO

OBJECTIVE: To assess the application value of mapping allele with resolved carrier status (MaReCs) technique for preimplantation genetic testing (PGT). METHODS: The characteristics of MaReCs for PGT and outcome of patients were retrospectively analyzed. RESULTS: Compared with those who could not use the technique, carriers who have used the MaReCs technique were younger, had significantly higher level of anti-Mullerian hormone, more antral follicles, occytes, mature occytes, biopsied embryos and euploid embryos, and lower risks for de novo chromosomal abnormality (P<0.05). It was necessary for couples with fewer oocytes, mature oocytes and balstocyst to preserve discarded embryos to facilitate the test. Carriers who have used the MaReCs technique had higher clinical pregnancy rate and abortion rate compared with those undergoing routine PGT, albeit no significant difference was found between the two groups (P> 0.05). Carriers undergoing MaReCs test could preferentially select embryos with normal chromosome structures for the transfer. CONCLUSION: Application of MaReCs has a prerequisite for having a minimum number of occytes and biopsied embryos and using discarded embryos sometimes. MaReCs is efficient for the detection of carrier status of embryos and attaining higher rate of pregnancy and live birth, which can significantly improve the outcome for couples carrying chromosomal translocations.


Assuntos
Diagnóstico Pré-Implantação , Translocação Genética , Alelos , Aneuploidia , Blastocisto , Feminino , Fertilização In Vitro , Testes Genéticos , Humanos , Gravidez , Estudos Retrospectivos
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 880-883, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487536

RESUMO

OBJECTIVE: To explore the genetic etiology of a fetus with autosomal recessive polycystic kidney disease (ARPKD). METHODS: Prenatal ultrasonography has revealed oligohydramnios and abnormal structure of fetal kidneys. After careful counseling, the couple opted induced abortion. With informed consent, genomic DNA was extracted from the muscle sample of the abortus and peripheral blood samples of the couple. High throughput whole exome sequencing was carried out to detect potential variants in relation with the disease. Suspected variants were verified by Sanger sequencing. RESULTS: Prenatal ultrasound revealed increased size of fetal kidneys, with multiple hyperechos from the right kidney, and multiple hyperechos with anechoic masses within the left kidney. DNA sequencing revealed that the fetus has carried heterozygous variants of the PKHD1 gene, including c.7994T>C inherited from its father, and two heterozygous variants of the PKHD1 gene c.5681G>A from its mother. CONCLUSION: The compound heterozygous c.7994T>C and c.5681G>A variants of the PKHD1 gene probably underlay the pathogenesis of ARPKD in this fetus. Above results can provide guidance for subsequent pregnancies of the couple.


Assuntos
Rim Policístico Autossômico Recessivo , Feminino , Feto , Testes Genéticos , Humanos , Mutação , Rim Policístico Autossômico Recessivo/diagnóstico por imagem , Rim Policístico Autossômico Recessivo/genética , Gravidez , Receptores de Superfície Celular/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 891-894, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487539

RESUMO

OBJECTIVE: To explore the genetic basis for a juvenile with maturity-onset diabetes of the young type 12(MODY12). METHODS: High-throughput sequencing was carried out to screen for the variants. Candidate variant was verified by Sanger sequencing. Pathogenity of the variant was predicted by searching the genetic databases and analysis by using bioinformatic software. RESULTS: Genetic testing indicated that the patient and his mother have both carried a heterozygous c.3976G>A variant (p.Glu1326Lys) in exon 32 of the ABCC8 gene. Prediction of the protein structure suggested the variant to be deleterious. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be uncertain significance. CONCLUSION: Whether the c.3976G>A variant of the ABCC8 gene is the cause of the disease in this patient or not depends on the functional studies and more case data. Above finding has enriched the spectrum of ABCC8 gene variants.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/genética , Testes Genéticos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
7.
BMC Pediatr ; 21(1): 387, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488686

RESUMO

BACKGROUND: The use of genome-wide sequencing in pediatric medicine and research is growing exponentially. While this has many potential benefits, the normative and empirical literature has highlighted various ethical issues. There have not been, however, any systematic reviews of these issues. The aim of this systematic review is to determine systematically the spectrum of ethical issues that is raised for stakeholders in in pediatric genome-wide sequencing. METHODS: A systematic review in PubMed and Google Books (publications in English or German between 2004 and 2021) was conducted. Further references were identified via reference screening. Data were analyzed and synthesized using qualitative content analysis. Ethical issues were defined as arising when a relevant normative principle is not adequately considered or when two principles come into conflict. RESULTS: Our literature search retrieved 3175 publications of which 143 were included in the analysis. Together these mentioned 106 ethical issues in pediatric genome-wide sequencing, categorized into five themes along the pediatric genome-wide sequencing lifecycle. Most ethical issues identified in relation to genome-wide sequencing typically reflect ethical issues that arise in general genetic testing, but they are often amplified by the increased quantity of data obtained, and associated uncertainties. The most frequently discussed ethical aspects concern the issue of unsolicited findings. CONCLUSION: Concentration of the debate on unsolicited findings risks overlooking other ethical challenges. An overarching difficulty presents the terminological confusion: both with regard to both the test procedure/ the scope of analysis, as well as with the topic of unsolicited findings. It is important that the genetics and ethics communities together with other medical professions involved work jointly on specific case related guidelines to grant the maximum benefit for the care of the children, while preventing patient harm and disproportionate overload of clinicians and the healthcare system by the wealth of available options and economic incentives to increase testing.


Assuntos
Atenção à Saúde , Testes Genéticos , Criança , Humanos
8.
J Coll Physicians Surg Pak ; 31(9): 1117-1119, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34500535

RESUMO

Familial amyloidotic polyneuropathy type 1 (FAP 1) is a systemic autosomal dominant amyloidosis, associated with transthyretin mutation. It is characterised by motor, autonomic and sensory neuropathy with relentless progression that results from amyloid deposition in different tissues. The authors describe the case of a patient with family history of a nephew, who underwent liver transplantation for unknown pathology, as well as the deaths of both his mother and a brother due to stroke. He reported complaints of dizziness, asthenia and sensory changes in the lower limbs and a history of arterial hypertension, dyslipidemia and chronic kidney disease. Physical examination revealed macroglossia and pain hyposensitivity in the anterior feet. In subsequent evaluation, the presence of proteinuria, changes in cardiac electrical conduction, sensory and motor neuropathy with sympathetic and parasympathetic dysfunction in electrophysiological study raised the suspicion of a systemic disease. The patient underwent kidney biopsy, which was positive for amyloid. FAP 1 diagnosis was later confirmed by genetic testing. Family history review confirmed that patient's liver transplanted nephew and other two nieces had FAP 1, which he was initially unaware of. Key Words: Familial amyloidotic polyneuropathy, Systemic amyloidosis, Transthyretin.


Assuntos
Neuropatias Amiloides Familiares/diagnóstico , Polineuropatias , Sistema Nervoso Autônomo , Testes Genéticos , Humanos , Masculino , Polineuropatias/diagnóstico , Pré-Albumina/genética
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1266-1270, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362514

RESUMO

OBJECTIVE: To analyze the genotypes and distribution of thalassemia in children in Quanzhou Region so as to provide reference for the prevention and control of thalassemia. METHODS: A total of 1 302 children with suspected thalassemia were collected from January 2014 to April 2020 in Quanzhou Region. The deletional α-thalassemia was detected by Gap-PCR, and DNA reverse dot blot (RDB) hybridization was used to detect α- and ß-thalassemia mutations. RESULTS: In the 1 302 cases, 667 cases were identified as thalassemia carriers, and the positive detection rate was about 51.23%. Among them, 380 cases of α-thalassemia gene were detected, and --SEA/αα was the most common genotype with the composition rate about 69.21%. Forty-two cases were identified as HbH disease, and -α3.7/--SEA was the most common genotype. While, 274 cases were identified as ß-thalassemia, and ßIVS-Ⅱ-654/ßN (35.40%) and ßCD41-42/ßN (33.94%) were the most common genotypes. Seventeen cases of ß-thalassemia major/intermedia were identified, and the most common genotypes were ßIVS-Ⅱ-654/ßIVS-Ⅱ-654 and ßIVS-Ⅱ-654/ßCD17. Meanwhile, 13 cases of α- complex ß- thalassemia were detected. Among them, 1 case of ß-thalassemia gene rare mutation Term CD+32 was firstly detected in Fujian Province, and 1 case of CD14-15 mutation was firstly detected in Quanzhou Region. In addition, 3 cases of abnormal hemoglobin disease were identified, in which 2 cases were Hb Q-Thailand and 1 case was Hb G-Honolulu. CONCLUSION: There are various genotypes of thalassemia in children in Quanzhou Region, and many children with thalassemia major or intermedia. Therefore, further prevention and control of thalassemia need to be strengthened for reducing the birth of thalassemia major or intermedia.


Assuntos
Talassemia alfa , Talassemia beta , Criança , China , Testes Genéticos , Genótipo , Heterozigoto , Humanos , Mutação , Talassemia alfa/genética , Talassemia beta/genética
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 719-722, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365609

RESUMO

OBJECTIVE: To analyze a pathogenic variant of MEFV gene in a family with autosomal dominant-familial Mediterranean fever (AD-FMF). METHODS: A 5-year-old boy presented with recurrent aseptic meningitis and his major symptoms included recurrent fever with headache and vomiting. His family members including his mother, sister and brother also had recurrent fever. A genetic disease was considered. DNAs were extracted from patient and all his family members' blood samples. Whole exome sequencing was performed to identify putative pathogenic variants that can explain this family's condition and Sanger sequencing was conducted. The impact of detected variants were predicted and validated by bioinformatics. RESULTS: A missense variant c.2229C>G (p.Phe743Leu) in MEFV gene was identified in the proband and his family members including his mother, sister and brother. This variant had not been reported in China previously, but the locus of it had already been reported in Arabic patient with AD-FMF (PS1). This variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on Mutationtaster, PROVEAN and PolyPhen-2. In addition, the change of amino acid, locating in 743 locus of pyrin protein, encoding by MEFV gene, was found to cause SPRY_PRY_TRIM20 and SPRY_superfamily domain destroyed and finally influenced the fuction of pyrin protein. On the other hand, using UCSF chimera software, we find the variant c.2229C>G (p.Phe743Leu) can induce serious influence to the spatial structure of pyrin protein and loss of protein fuction (PP3). According to the ACMG variant classification guideline, the variant c.2229C>G (p.Phe743Leu) in MEFV gene was classified as likely pathogenic (PS1+PM2+PP3). CONCLUSION: The condition of this AD-FMF family may be attributed to the missense variant c.2229C>G (p.Phe743Leu) in MEFV gene. The recurrent aseptic meningitis was a very rare manifestation in AD-FMF patients and had not been reported in China previously. The clinical and genetic findings of the present study are helpful for the further understanding of AD-FMF.


Assuntos
Febre Familiar do Mediterrâneo , Pré-Escolar , Febre Familiar do Mediterrâneo/genética , Frequência do Gene , Testes Genéticos , Humanos , Masculino , Mutação , Pirina/genética , Sequenciamento Completo do Exoma
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 768-770, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365621

RESUMO

OBJECTIVE: To carry out genetic testing for a pregnant woman with mild mental retardation, facial dysmorphism, and a history of adverse pregnancies and provide prenatal diagnosis for her. METHODS: Routine G-banded karyotyping and single nucleotide polymorphism microarray (SNP-array) analysis were performed on the couple and amniotic fluid sample. RESULTS: No karyotypic abnormality was found with the couple and amniotic fluid sample. SNP-array analysis showed that the woman has carried a 7.801 Mb microdeletion in 10q22.3q23.2, which involved 18 OMIM genes including CDHR1, BMPR1A, NRG3, GRID1 and LDB3, which are associated with facial abnormalities, developmental retardation, mental retardation and autism. The fetus also carried a 7.819 Mb deletion in the same region, while the father showed no abnormality. CONCLUSION: Both the pregnant woman and her fetus have carried a 10q22.3q23.2 microdeletion, which has provided guidance for her subsequent pregnancy.


Assuntos
Testes Genéticos , Diagnóstico Pré-Natal , Caderinas , Bandeamento Cromossômico , Deleção Cromossômica , Feminino , Feto , Humanos , Cariotipagem , Proteínas do Tecido Nervoso , Gravidez
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 775-778, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365623

RESUMO

OBJECTIVE: To explore the clinical feature, diagnosis and phenotype of Majeed syndrome. METHODS: Clinical manifestation, diagnostic process, imaging feature and genetic testing of an ethnic Han Chinese patient with Majeed syndrome were reviewed. RESULTS: The patient, a 3-year-9-month-old boy, had featured psychomotor retardation and developed bone pain from 8 month on. The child had tenderness of the lower limbs and presented with repeatedly joint swelling and pain accompanied by fever. Physical signs included limb muscle weakening, slightly decreased muscle tone, reduced muscle volume and positive Gower sign. High-throughput sequencing revealed that the child has carried compound heterozygous variants of the LPIN2 gene, including c.1966A>G and c.2534delG. MRI showed multiple lesions in bilateral knee joints and distal middle tibia presenting as patchy SPAIR high signals with unclear edge, in addition with edema of soft tissue surrounding the right distal femur. CONCLUSION: Majeed syndrome is characterized by chronic and recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and growth retardation. Surrounding muscle tissue of osteomyelitis may also be involved. The syndrome may also affect the central nervous system, resulting in delayed language and motor development. Discovery of multiple pathological variants of the LPIN2 gene suggested that the clinical phenotype of this syndrome may vary between patients to some extent.


Assuntos
Anemia Diseritropoética Congênita , Síndromes de Imunodeficiência , Osteomielite , Anemia Diseritropoética Congênita/genética , Criança , Testes Genéticos , Humanos , Síndromes de Imunodeficiência/genética , Lactente , Masculino , Osteomielite/genética
13.
Zhonghua Zhong Liu Za Zhi ; 43(8): 843-849, 2021 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-34407589

RESUMO

Objective: To evaluate the value of next generation sequencing (NGS) in the genetic testing of Lynch syndrome. Methods: Immunohistochemical method was used to detect the expressions of DNA mismatch repair (MMR) proteins, including MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) in colorectal cancer, gastric cancer and endometrial cancer tissues collected from Shandong Provincial Hospital between 2016 and 2018. The genomic DNA of 45 patients who were suspected with Lynch syndrome was extracted from non-cancerous tissue paraffin samples, which were postoperatively confirmed by microscope. The mutations of 12 genes including MLH1 and MSH2 were detected using NGS. The germline mutant sites and significance were analyzed by bioinformatics technology and further confirmed by using Sanger sequencing. Results: The immunohistochemical results showed that the 45 cases of suspected Lynch syndrome included 22 cases of MLH1 and PMS2 deficient expression, 16 cases of MLH2 and MSH6 deficient expression, and 7 cases of MMR proteins normal expression. The NGS result showed that 28 cases of adjacent sample from colon cancer patients included 4 cases of MLH1 pathogenic mutation, 1 case of suspected MLH1 mutation, 2 cases of MLH2 pathogenic mutation, 2 cases of suspected MLH2 mutation. No MMR gene mutation was found in adjacent samples of 6 cases of rectal cancer, 6 cases of gastric cancer and 7 cases of colorectal cancer with MMR normal expression. One case of MLH1 or MHL2 pathogenic mutation and one case of MLH1 suspected mutation was detected in adjacent samples of 5 cases of endometrial cancer. Moreover, NGS also detected many other genes mutations and unreported gene mutation sites. Pathogenic and suspected MLH1 and MSH2 mutations were verified by Sanger sequencing. Conclusions: High-throughput NGS is a quick, accurate and reliable technique to identify gene variants in suspected Lynch syndrome patients. It has a wide application prospect for gene testing of tumors associated with Lynch syndrome.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Feminino , Testes Genéticos , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Instabilidade de Microssatélites , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-34444499

RESUMO

With the increasing number of cancer cases worldwide, genetic testing for familiar cancers seems inevitable, yet little is known on population interest and the monetary value for cancer genetic risk information. The current study aimed to determine the willingness to undergo and pay for cancer genetic testing among the Malaysian population. A self-administered questionnaire was distributed to cancer patients and their family members in the oncology and daycare units in several government hospitals. Of 641 respondents (354 patients, 287 family members), 267 (41.7%) were willing to undergo cancer genetic testing. The median that respondents were willing to pay was USD 48.31 (MYR 200.00) IQR USD 96.91 (MYR 400), while 143 (22.3%) respondents were willing to pay a shared cost with the insurance company. Regression analysis identified independent positive predictors of willingness to pay as respondent's status as a family member, high education level, and willingness to undergo cancer genetic testing in general, while in patients, female gender and high level of education were identified as independent positive predictors. Generally, the population needs more information to undergo and pay for cancer genetic testing. This will increase the utilization of the services offered, and with cost-sharing practices with the provider, it can be implemented population-wide.


Assuntos
Testes Genéticos , Neoplasias , Custo Compartilhado de Seguro , Família , Feminino , Humanos , Neoplasias/genética , Inquéritos e Questionários
15.
Adv Exp Med Biol ; 1288: 161-173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34453736

RESUMO

Non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) are two common causes of infertility that affect a considerable number of men. However, few studies were performed to understand the molecular etiology of these disorders. Studies based on bioinformatics and genetic analyses in recent years, however, have yielded insightful information and have identified a number of genes that are involved in these disorders. In this review, we briefly summarize and evaluate these findings. We also discuss findings based on epigenetic modifications of sperm DNAs that affect a number of genes pertinent to NOA and OA. The information summarized in this Chapter should be helpful to investigators in future functional studies of NOA and OA.


Assuntos
Azoospermia , Infertilidade Masculina , Azoospermia/genética , Testes Genéticos , Humanos , Infertilidade Masculina/genética , Masculino , Espermatozoides , Testículo
16.
Pan Afr Med J ; 39: 72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422195

RESUMO

Introduction: Fanconi anemia (FA) is a rare inherited hematological disease due to a defect in the DNA repair pathway resulting in congenital abnormalities and high susceptibility to develop cancers. The cytogenetic analysis using alkylating agents is still a reference test to establish the diagnosis. Despite the genetic heterogeneity, the identification of the causal mutation is actually performed especially after the development of next generation sequencing (NGS). Methods: we report here nine Moroccan patients referred to the department of Medical Genetics for suspicion of FA. We realized a genetic consultation to establish a clinical record with biological data before carrying out the genetic analysis. Karyotyping with mitomycin was performed for all the probands before elaborating molecular study. We used massively parallel sequencing to analyse the three most frequent mutated genes FANCA, FANCC, and FANCG, representing 84% of all genes involved in FA. Results: all the patients showed hematological signs associated with at least one extra-hematological congenital anomaly. The chromosomal breaks were significantly higher for the nine patients, compared to the controls. The molecular diagnosis was confirmed in 8 of the 9 families tested (88.8%) with 4 novel mutations. The next generation based sequencing identified 9 variations: 6 in the FANCA gene (66.6%), 3 in the FANCG gene (33.3%) and no FANCC variation was found. Of those, 7 were homozygous and 2 were compounds heterozygous. Conclusion: to the best of our knowledge, this is the first molecular report of Moroccan patients with FA suggesting the predominance of two genes without any recurrent mutation. The molecular analysis of FANCA and FANCG genes should be offered first for all patients in Morocco.


Assuntos
Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação G da Anemia de Fanconi/genética , Anemia de Fanconi/diagnóstico , Criança , Pré-Escolar , Análise Citogenética , Anemia de Fanconi/genética , Proteína do Grupo de Complementação C da Anemia de Fanconi/genética , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Marrocos , Mutação
17.
Artigo em Inglês | MEDLINE | ID: mdl-34444091

RESUMO

Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. Approximately 3-5% of CRCs are associated with hereditary cancer syndromes. Individuals who harbor germline mutations are at an increased risk of developing early onset CRC, as well as extracolonic tumors. Genetic testing can identify genes that cause these syndromes. Early detection could facilitate the initiation of targeted prevention strategies and surveillance for CRC patients and their families. The aim of this study was to determine the cost-effectiveness of CRC genetic testing. We utilized a cross-sectional design to determine the cost-effectiveness of CRC genetic testing as compared to the usual screening method (iFOBT) from the provider's perspective. Data on costs and health-related quality of life (HRQoL) of 200 CRC patients from three specialist general hospitals were collected. A mixed-methods approach of activity-based costing, top-down costing, and extracted information from a clinical pathway was used to estimate provider costs. Patients and family members' HRQoL were measured using the EQ-5D-5L questionnaire. Data from the Malaysian Study on Cancer Survival (MySCan) were used to calculate patient survival. Cost-effectiveness was measured as cost per life-year (LY) and cost per quality-adjusted life-year (QALY). The provider cost for CRC genetic testing was high as compared to that for the current screening method. The current practice for screening is cost-saving as compared to genetic testing. Using a 10-year survival analysis, the estimated number of LYs gained for CRC patients through genetic testing was 0.92 years, and the number of QALYs gained was 1.53 years. The cost per LY gained and cost per QALY gained were calculated. The incremental cost-effectiveness ratio (ICER) showed that genetic testing dominates iFOBT testing. CRC genetic testing is cost-effective and could be considered as routine CRC screening for clinical practice.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Análise Custo-Benefício , Estudos Transversais , Testes Genéticos , Humanos , Anos de Vida Ajustados por Qualidade de Vida
18.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360727

RESUMO

Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient's family was advised to undergo genetic counseling to consider additional RCC screening.


Assuntos
Fumarato Hidratase/deficiência , Deleção de Genes , Mutação em Linhagem Germinativa , Leiomiomatose/genética , Erros Inatos do Metabolismo/genética , Hipotonia Muscular/genética , Síndromes Neoplásicas Hereditárias/genética , Transtornos Psicomotores/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Adulto , Feminino , Fumarato Hidratase/genética , Testes Genéticos , Humanos
19.
Pan Afr Med J ; 38: 350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367429

RESUMO

Introduction: sickle cell disease is one of the greatest public health problems of this age. This study was conducted to assess the knowledge, attitude and control practices on sickle cell disease (SCD) among selected secondary school students in Osun State, Nigeria. Methods: a descriptive cross-sectional study involved 420 secondary school students within Osogbo Metropolis selected by a multistage stratified sampling technique, using self-administered structured questionnaire. Data were collected using pre-tested self-administered semi structured questionnaire. Data were analyzed using SPSS version 20. Results: a total of 420 students were interviewed, modal age range 15-20 years. There were more females (55%) than males (45%). Majority of them were christians (57.1%). A larger percentage of the respondents were aware of SCD (58.5%). However, comprehensive knowledge as regards the various genotypes related to SCD, tests to be done for genotype screening among the respondents is low. One third of the respondents had positive attitude towards SCD (65%) and nearly one half (48%) of the respondents had bad control practices. Conclusion: findings in this study shows a high level of general awareness on SCD, even though comprehensive knowledge as regards the various genotype related to SCD, tests to be done for genotype screening among others is low. The need to improve on their attitude and practice towards the disease is highly recommended because having a good knowledge is not as important as applying the knowledge in a way to stop the spread of the disease.


Assuntos
Anemia Falciforme/prevenção & controle , Testes Genéticos/métodos , Conhecimentos, Atitudes e Prática em Saúde , Estudantes/estatística & dados numéricos , Adolescente , Anemia Falciforme/genética , Criança , Estudos Transversais , Feminino , Genótipo , Humanos , Masculino , Nigéria , Inquéritos e Questionários , Adulto Jovem
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 787-790, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365626

RESUMO

OBJECTIVE: To explore the genetic basis for a sib pair featuring 17beta-hydroxysteroid dehydrogenase type 3 deficiency. METHODS: Genomic DNA was extracted from the proband, her sister, and their parents, and was subjected to sequencing analysis with a gene panel for sexual development. Suspected variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: Both the proband and her sister were found to harbor novel compound heterozygous missense variants of the HSD17B3 gene, namely c.839T>C (p.Leu280Pro) and c.239G>T (p.Arg80Leu), which were derived respectively from their mother and father. The variants were unreported previously and predicted to be deleterious by PolyPhen2, MutationTaster and other online software. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.839T>C(p.Leu280Pro) and c.239G>T (p.Arg80Leu) were predicted to be likely pathogenic (PM2+PP1+PP2+PP3+PP4, PM2+PM5+PP1+PP2+PP3+PP4). CONCLUSION: The compound heterogeneous variants of the HSD17B3 gene probably underlay the disease in this sib pair. 17beta-hydroxysteroid dehydrogenase type 3 deficiency may lack specific clinical features and laboratory index, genetic testing can facilitate a definitive diagnosis.


Assuntos
Testes Genéticos , Genômica , 17-Hidroxiesteroide Desidrogenases/genética , Feminino , Humanos , Mutação , Mutação de Sentido Incorreto
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