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1.
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
2.
Exp Suppl ; 111: 21-27, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588525

RESUMO

Increasing data about the human genome and associations between certain genetic regions with various conditions and diseases positioned human genetics at the top of the most emerging fields in medicine. Many diagnostics algorithms and therapeutical approaches used in everyday practice are based on genetic data. Molecular genetic diagnostics covered by this book uses genetic data obtained using germline DNA. In this book, the role of somatic mutation testing will be not covered; however, in many chapters, i.e., on hereditary tumor syndromes, the role of somatic mutations as the second hit for tumorigenesis will be mentioned. Genetic variants (genotypes) identified in germline DNA are responsible for transmission of diseases (phenotypes). This chapter will briefly summarize classical inheritance patterns. Most of the heritable human diseases are transmitted in an autosomal recessive way, but others, i.e., inherited tumor syndromes, follow the autosomal dominant pattern. Nomenclature used for pedigree analysis as well as the main features of inheritance patterns are also briefly reviewed.


Assuntos
Carcinogênese/genética , DNA , Padrões de Herança , Neoplasias/genética , Genótipo , Humanos , Linhagem
3.
Hereditas ; 156: 31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31548836

RESUMO

Background: Cleidocranial dysplasia (CCD) is a rare autosomal dominant disorder mainly characterized by hypoplastic or absent clavicles, delayed closure of the fontanelles, multiple dental abnormalities, and short stature. Runt-related transcription factor 2 (RUNX2) gene variants can cause CCD, but are not identified in all CCD patients. Methods: In this study, we detected genetic variants in seven unrelated children with CCD by targeted high-throughput DNA sequencing or Sanger sequencing. Results: All patients carried a RUNX2 variant, totally including three novel pathogenic variants (c.722_725delTGTT, p.Leu241Serfs*8; c.231_232delTG, Ala78Glyfs*82; c.909C > G, p.Tyr303*), three reported pathogenic variants (c.577C > T, p.Arg193*; c.574G > A, p.Gly192Arg; c.673 C > T, p.Arg225Trp), one likely pathogenic variant (c.668G > T, p.Gly223Val). The analysis of the variant source showed that all variants were de novo except the two variants (c.909C > G, p.Tyr303*; c.668G > T, p.Gly223Val) inherited from the patient's father and mother with CCD respectively. Further bioinformatics analysis indicated that these variants could influence the structure of RUNX2 protein by changing the number of H-bonds or amino acids. The experimental result showed that the Gly223Val mutation made RUNX2 protein unable to quantitatively accumulate in the nucleus. Conclusions: The present study expands the pathogenic variant spectrum of RUNX2 gene, which will contribute to the diagnosis of CCD and better genetic counseling in the future.


Assuntos
Displasia Cleidocraniana/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Núcleo Celular , Criança , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Mutação , Linhagem
4.
Hum Genet ; 138(10): 1183-1200, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471722

RESUMO

The glutamate pyruvate transaminase 2 (GPT2) gene produces a nuclear-encoded mitochondrial enzyme that catalyzes the reversible transfer of an amino group from glutamate to pyruvate, generating alanine and alpha-ketoglutarate. Recessive mutations in GPT2 have been recently identified in a new syndrome involving intellectual and developmental disability (IDD), postnatal microcephaly, and spastic paraplegia. We have identified additional families with recessive GPT2 mutations and expanded the phenotype to include small stature. GPT2 loss-of-function mutations were identified in four families, nine patients total, including: a homozygous mutation in one child [c.775T>C (p.C259R)]; compound heterozygous mutations in two siblings [c.812A>C (p.N271T)/c.1432_1433delGT (p.V478Rfs*73)]; a novel homozygous, putative splicing mutation [c.1035C>T (p.G345=)]; and finally, a recurrent mutation, previously identified in a distinct family [c.1210C>T (p.R404*)]. All patients were diagnosed with IDD. A majority of patients had remarkably small stature throughout development, many < 1st percentile for height and weight. Given the potential biological function of GPT2 in cellular growth, this phenotype is strongly suggestive of a newly identified clinical susceptibility. Further, homozygous GPT2 mutations manifested in at least 2 of 176 families with IDD (approximately 1.1%) in a Pakistani cohort, thereby representing a relatively common cause of recessive IDD in this population, with recurrence of the p.R404* mutation in this population. Based on variants in the ExAC database, we estimated that approximately 1 in 248 individuals are carriers of moderately or severely deleterious variants in GPT2.


Assuntos
Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Genes Recessivos , Predisposição Genética para Doença , Mutação , Fenótipo , Transaminases/genética , Adolescente , Alelos , Substituição de Aminoácidos , Deficiências do Desenvolvimento/metabolismo , Ativação Enzimática , Éxons , Feminino , Frequência do Gene , Estudos de Associação Genética , Genética Populacional , Genótipo , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Imagem por Ressonância Magnética , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Modelos Moleculares , Linhagem , Conformação Proteica , Sítios de Splice de RNA , Análise de Sequência de DNA , Relação Estrutura-Atividade , Transaminases/química , Transaminases/metabolismo
5.
Ideggyogy Sz ; 72(7-8): 273-277, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31517460

RESUMO

Cerebral cavernous malformations (CCMs) represent a relatively rare and heterogeneous clinical entity with mutations identified in three genes. Both sporadic and familial forms have been reported. We present a young female patient with episodic paresthesia and headaches, but without acute neurological deficits. Her mother had a hemorrhaged cavernoma surgically removed 21 years ago. Cranial magnetic resonance imaging revealed multiple cavernous malformations in the size of a few millimeters and the ophthalmologic exam detected retinal blood vessel tortuosity in the proband. Targeted exome sequencing analysis identified a nonsense mutation in exon 16 of the KRIT1 gene, which resulted in a premature stop codon and a truncated protein underlying the abnormal development of cerebral and retinal blood vessels. This mutation with pathogenic significance has been reported before. Our case points to the importance of a thorough clinical and molecular work up despite the uncertain neurological complaints, since life style recommendations, imaging monitoring and genetic counseling may have major significance in the long term health of the patient.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Proteína KRIT1/genética , Vasos Retinianos/diagnóstico por imagem , Feminino , Cefaleia/etiologia , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Humanos , Imagem por Ressonância Magnética , Mutação , Parestesia/etiologia , Linhagem , Deleção de Sequência/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 877-881, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515780

RESUMO

OBJECTIVE: To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD). METHODS: Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees. RESULTS: Gene sequencing has identified a homozygous c.985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c.1459_1467del9 (p.D487_F489del) and c.1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c.985_987delTACinsAA(Y329Kfs) mutation. CONCLUSION: Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c.985_987delTACinsAA(Y329Kfs) is the most common. The c.1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Esteroide 17-alfa-Hidroxilase/genética , Éxons , Feminino , Humanos , Masculino , Mutação , Linhagem
7.
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
8.
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
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 897-900, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515785

RESUMO

OBJECTIVE: To explore the genetic basis for a case of recurrent fetal congenital hydrocephalus. METHODS: Next-generation sequencing was carried out for the fetus, the gravida and two of her sisters. RESULTS: The fetus was found to harbor a c.1765T>C (p.Tyr589His) mutation in exon 14 of the L1CAM gene, which was derived from the gravida. CONCLUSION: Male fetuses with recurrent hydrocephalus should be subjected to testing of the L1CAM gene to facilitate genetic counseling and prenatal diagnosis.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Hidrocefalia/genética , Molécula L1 de Adesão de Célula Nervosa/genética , Análise Mutacional de DNA , Feminino , Feto , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Hidrocefalia/diagnóstico , Masculino , Mutação , Linhagem , Gravidez
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 901-904, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515786

RESUMO

OBJECTIVE: To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. METHODS: Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. RESULTS: The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c.92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. CONCLUSION: The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.


Assuntos
Afibrinogenemia/genética , Fibrinogênio/genética , Afibrinogenemia/congênito , Análise Mutacional de DNA , Feminino , Humanos , Mutação , Linhagem , Fenótipo
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 905-909, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515787

RESUMO

OBJECTIVE: To detect mutation of LBR gene in a pedigree affected with Pelger-Huёt anomaly (PHA) and to explore its clinical characteristics. METHODS: Genomic DNA was extracted from the pedigree and healthy controls. The 14 exons of the LBR gene were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified in other family members and 100 healthy controls. Polyphen-2 and SIFT software were used to predict the effect of the mutation, and Swiss-model software was used to simulate the protein structure. RESULTS: Three patients were found to carry a c.893G>A mutation in exon 8 of the LBR gene, which resulted in substitution of the 298th amino acid residue glycine by glutamic acid (p.Gly298Glu). The same mutation was not found in healthy family members and 100 healthy controls. The mutation was predicted to be damaging. Bioinformatic simulation showed the mutation has altered the 3D structure of the LBR protein. CONCLUSION: The c.893G>A (p.Gly298Glu) mutation in the LBR gene probably underlies the PHA in this pedigree and has enriched the spectrum of LBR gene mutations.


Assuntos
Anomalia de Pelger-Huët/genética , Receptores Citoplasmáticos e Nucleares/genética , Estudos de Casos e Controles , Análise Mutacional de DNA , Éxons , Humanos , Mutação , Linhagem , Reação em Cadeia da Polimerase
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 914-917, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515789

RESUMO

OBJECTIVE: To explore the genetic basis of a child with chronic kidney disease featuring renal shrinkage and creatinine increase. METHODS: Peripheral venous blood samples were taken from the child, his brother and two parents and subjected to whole exome sequencing. Suspected mutations were verified by Sanger sequencing. Bioinformatic analysis was carried out to predict the influence of mutations on the structure and function of the protein product. RESULTS: High-throughput and Sanger sequencing revealed that the child has carried compound heterozygous mutations of the COL4A4 gene, namely c.4550T>G in exon 47 (inherited from his mother) and c.199C>T in exon 5 (inherited from his father). Neither mutation was reported previously. Bioinformatic analysis showed that both mutations have located in highly conserved regions. The same mutations were not found in his brother. CONCLUSION: The compound heterozygous c.4550T>G and c.199C>T mutations probably underlie the disease in this child. The findings have enriched the mutation spectrum of the COL4A4 gene.


Assuntos
Colágeno Tipo IV/genética , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/genética , Criança , Éxons , Feminino , Humanos , Masculino , Mutação , Linhagem , Sequenciamento Completo do Exoma
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 918-921, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515790

RESUMO

OBJECTIVE: To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy. METHODS: Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband. RESULTS: The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c.341G>A (p.G114D) mutation in exon 2 of the INF2 gene. CONCLUSION: The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c.341G>A mutation of the INF2 gene.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Glomerulosclerose Segmentar e Focal/genética , Proteínas dos Microfilamentos/genética , Doença de Charcot-Marie-Tooth/complicações , Criança , Feminino , Glomerulosclerose Segmentar e Focal/complicações , Heterozigoto , Humanos , Masculino , Mutação , Linhagem
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 926-929, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515792

RESUMO

OBJECTIVE: To explore the genetic basis of a neonate with argininosuccinic aciduria (ASA). METHODS: A neonate with lethargy and food refusal was admitted. The patient had myoclonus, myasthenia, uroschesis, irregular breathing and paroxysmal ventricular tachycardia, and died at 75 hours after birth. Laboratory test showed marked increase in blood ammonia (1249.8 µmol/L). Peripheral blood samples of the patient, her parents and sister were collected and subjected to trio whole-exome sequencing. RESULTS: Whole-exome sequencing revealed that the patient has carried compound heterozygous mutations of the argininosuccinate lyase (ASL) gene, namely c.425(exon5)_c.426(exon5) insAGCTCCCAGCT (p.Thr142Thrfs*37) and c.626(exon8)delT (p.Leu209Argfs*42). The patient was diagnosed as ASA caused by ASL gene mutations. Her parents and her elder sister were heterozygous carriers of the above mutations and had a normal phenotype. CONCLUSION: ASA is a severe congenital genetic metabolic disease and can manifest as onset of hyperammonemia in neonates. The clinical diagnosis is difficult and ASL gene testing may be helpful.


Assuntos
Argininossuccinato Liase/genética , Acidúria Argininossuccínica/diagnóstico , Acidúria Argininossuccínica/genética , Hiperamonemia , Feminino , Testes Genéticos , Humanos , Recém-Nascido , Linhagem
15.
Genet Sel Evol ; 51(1): 44, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412777

RESUMO

BACKGROUND: Experimental intercrosses between outbred founder populations are powerful resources for mapping loci that contribute to complex traits i.e. quantitative trait loci (QTL). Here, we present an approach and its accompanying software for high-resolution reconstruction of founder mosaic genotypes in the intercross offspring from such populations using whole-genome high-coverage sequence data on founder individuals (~ 30×) and very low-coverage sequence data on intercross individuals (< 0.5×). Sets of founder-line informative markers were selected for each full-sib family and used to infer the founder mosaic genotypes of the intercross individuals. The application of this approach and the quality of the estimated genome-wide genotypes are illustrated in a large F2 pedigree between two divergently selected lines of chickens. RESULTS: We describe how we obtained whole-genome genotype data for hundreds of individuals in a cost- and time-efficient manner by using a Tn5-based library preparation protocol and an imputation algorithm that was optimized for this application. In total, 7.6 million markers segregated in this pedigree and, within each full-sib family, between 10.0 and 13.7% of these were fully informative, i.e. fixed for alternative alleles in the founders from the divergent lines, and were used for reconstruction of the offspring mosaic genotypes. The genotypes that were estimated based on the low-coverage sequence data were highly consistent (> 95% agreement) with those obtained using individual single nucleotide polymorphism (SNP) genotyping. The estimated resolution of the inferred recombination breakpoints was relatively high, with 50% of them being defined on regions shorter than 10 kb. CONCLUSIONS: A method and software for inferring founder mosaic genotypes in intercross offspring from low-coverage whole-genome sequencing in pedigrees from heterozygous founders are described. They provide high-quality, high-resolution genotypes in a time- and cost-efficient manner. The software is freely available at https://github.com/CarlborgGenomics/Stripes .


Assuntos
Galinhas/genética , Técnicas de Genotipagem , Sequenciamento Completo do Genoma , Animais , Cruzamento , Custos e Análise de Custo , Cruzamentos Genéticos , Conjuntos de Dados como Assunto , Feminino , Efeito Fundador , Técnicas de Genotipagem/economia , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único , Software , Sequenciamento Completo do Genoma/economia
16.
BMC Ophthalmol ; 19(1): 191, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438893

RESUMO

BACKGROUND: To investigate the efficacy and safety of repeated phototherapeutic keratectomies (PTKs) during long-term treatment for corneal dystrophy (CD) in a Chinese pedigree carrying the R124L mutation in TGFBI. METHODS: This was a retrospective review of 20-year medical and genetic records involving five CD patients (10 eyes) from one pedigree. During this period, PTK was conducted for an eye when best-corrected distance visual acuity (BCDVA) reached > 1.0 (LogMAR), due to either primary or recurrent opacities in the cornea. All PTKs were performed by 193-nm excimer laser with or without creation of epithelial flaps. For each eye, routine measurements were conducted for the number of PTKs during follow-up, mean time to recurrence, and BCDVA pre- and post- every PTK (measurements within 3 months from each PTK). Corneal thicknesses measured after the last PTK and at the last visit were analyzed, and subjective satisfaction was assessed. RESULTS: Gene testing revealed an R124L mutation in TGFBI. During 19.60 ± 1.78 years of follow-up, PTKs were conducted twice for three eyes, three times for six eyes, and four times for one eye. After each PTK, effective visual acuity was maintained for 3.60 ± 1.12 years before significant recurrence. BCDVA improved significantly postoperatively than preoperatively for the first PTK for each eye (p < 0.001), as well as the second (p < 0.001) and third one (p < 0.001). After the last PTK and at the final visit, the thinnest corneal thickness was 371.50 ± 56.47 µm and 358.40 ± 101.11 µm, respectively. The average subjective satisfaction score was 8.60 ± 0.89. CONCLUSIONS: Multiple repeated PTKs were effective and safe in a long-term study of CD patients with an R124L mutation in TGFBI.


Assuntos
Córnea/cirurgia , Distrofias Hereditárias da Córnea/cirurgia , Proteínas da Matriz Extracelular/genética , Previsões , Lasers de Excimer/uso terapêutico , Mutação , Ceratectomia Fotorrefrativa/métodos , Fator de Crescimento Transformador beta/genética , Adulto , Idoso , China/epidemiologia , Córnea/patologia , Distrofias Hereditárias da Córnea/epidemiologia , Distrofias Hereditárias da Córnea/genética , DNA/genética , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Estudos Retrospectivos , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento , Acuidade Visual
17.
Arch Endocrinol Metab ; 63(4): 369-375, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365623

RESUMO

OBJECTIVE: Paraganglioma (PGL) and pheochromocytoma (PCC) are rare neuroendocrine tumors that were considered to be predominantly sporadic. However, with the identification of novel susceptibility genes over the last decade, it is currently estimated that up to 40% of cases can occur in the context of a hereditary syndrome. We aimed to characterize PGL/PCC families to exemplify the different scenarios in which hereditary syndromes can be suspected and to emphasize the importance for patients and their families of making an opportune genetic diagnosis. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with PGL/PCC. Germline mutations were studied using next-generation sequencing panels including SDHA, SDHB, SDHC and SDHD. Clinical data were collected from clinical records, and all patients received genetic counseling. RESULTS: We describe 4 families with PGL/PCC and germline mutations in SDH complex genes. 2 families have SDHB mutations and 2 SDHD mutations. The clinical presentation of the patients and their families was heterogeneous, with some being atypical according to the literature. CONCLUSIONS: PGL/PCC are more commonly associated with a germline mutation than any other cancer type, therefore, all individuals with these types of tumors should undergo genetic risk evaluation. NGS multigene panel testing is a cost-effective approach given the overlapping phenotypes. Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical and imaging surveillance and their families should undergo genetic counseling. For all these reasons, it is critical that all medical staff can suspect and diagnose these inherited cancer predisposition syndromes.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Mutação em Linhagem Germinativa/genética , Paraganglioma/genética , Feocromocitoma/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Masculino , Linhagem , Estudos Retrospectivos , Vigilância de Evento Sentinela
18.
Arch Endocrinol Metab ; 63(4): 385-393, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365626

RESUMO

INTRODUCTION: Gigantism is a rare pediatric disease characterized by increased production of growth hormone (GH) before epiphyseal closure, that manifests clinically as tall stature, musculoskeletal abnormalities, and multiple comorbidities. MATERIALS AND METHODS: Case series of 6 male patients with gigantism evaluated at the Endocrinology Service of Hospital de San José (Bogotá, Colombia) between 2010 and 2016. RESULTS: All patients had macroadenomas and their mean final height was 2.01 m. The mean age at diagnosis was 16 years, and the most common symptoms were headache (66%) and hyperhidrosis (66%). All patients had acral changes, and one had visual impairment secondary to compression of the optic chiasm. All patients underwent surgery, and 5 (83%) required additional therapy for biochemical control, including radiotherapy (n = 4, 66%), somatostatin analogues (n = 5, 83%), cabergoline (n = 3, 50%), and pegvisomant (n = 2, 33%). Three patients (50%) achieved complete biochemical control, while 2 patients showed IGF-1 normalization with pegvisomant. Two patients were genetically related and presented a mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene (pathogenic variant, c.504G>A in exon 4, p.Trp168*), fulfilling the diagnostic criteria of familial isolated pituitary adenoma. CONCLUSIONS: This is the largest case series of patients with gigantism described to date in Colombia. Transsphenoidal surgery was the first-choice procedure, but additional pharmacological therapy was usually required. Mutations in the AIP gene should be considered in familial cases of GH-producing adenomas.


Assuntos
Adenoma/terapia , Gigantismo/terapia , Neoplasias Hipofisárias/terapia , Adenoma/diagnóstico , Adolescente , Colômbia , Seguimentos , Gigantismo/diagnóstico , Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Humanos , Fator de Crescimento Insulin-Like I/análise , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Mutação/genética , Linhagem , Neoplasias Hipofisárias/diagnóstico , Estudos Retrospectivos , Distribuição por Sexo , Resultado do Tratamento , Adulto Jovem
19.
Oecologia ; 191(2): 349-358, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463783

RESUMO

A prime example of plant-animal interactions is the interaction between plants and pollinators, which typically receive nectar and/or pollen as reward for their pollination service. While nectar provides mostly carbohydrates, pollen represents the main source of protein and lipids for many pollinators. However, the main function of pollen is to carry nutrients for pollen tube growth and thus fertilization. It is unclear whether pollinator attraction exerts a sufficiently strong selective pressure to alter the nutritional profile of pollen, e.g., through increasing its crude protein content or protein-to-lipid ratio, which both strongly affect bee foraging. Pollen nutritional quality may also be merely determined by phylogenetic relatedness, with pollen of closely related plants showing similar nutritional profiles due to shared biosynthetic pathways or floral morphologies. Here, we present a meta-analysis of studies on pollen nutrients to test whether differences in pollen nutrient contents and ratios correlated with plant insect pollinator dependence and/or phylogenetic relatedness. We hypothesized that if pollen nutritional content was affected by pollinator attraction, it should be different (e.g., higher) in highly pollinator-dependent plants, independent of phylogenetic relatedness. We found that crude protein and the protein-to-lipid ratio in pollen strongly correlated with phylogeny. Moreover, pollen protein content was higher in plants depending mostly or exclusively on insect pollination. Pollen nutritional quality thus correlated with both phylogenetic relatedness and pollinator dependency, indicating that, besides producing pollen with sufficient nutrients for reproduction, the nutrient profile of zoophilous plants may have been shaped by their pollinators' nutritional needs.


Assuntos
Nutrientes , Polinização , Animais , Abelhas , Flores , Linhagem , Filogenia , Pólen
20.
Yi Chuan ; 41(8): 716-724, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447422

RESUMO

In order to investigate the genetic variations and the clinical manifestations of a range of congenital ectrodactyly family and to summarize the split hand/foot malformation (SHFM) types and their related pathogenic genes, we conducted phenotypic analyses of patient's limbs by physical and X-ray examination. The haplotypes were analyzed by using the extracted genes from peripheral blood on D10S1709, D10S192, D10S597, D10S1693 and D10S587 loci, and the mutation duplication loci were confirmed by Array-CGH detection. The pathogenic factors and inheritance pattern of SHFM were analyzed based on family investigation and gene analysis. Results demonstrate the proband's phenotype is typically of a congenital SHFM which is manifested by missing bilateral index and middle fingers, short bilateral thumbs, deformed left ring finger with webbing of the skin missing at the middle finger; bilateral big toe with the second and the third toe missing, fourth and fifth toe fusion leading to a deformed toe separated from the first toe by the middle of the foot. The haplotype analyses show that there is a repeat of at least 610 kb in chromosome 10q24.31-10q24.32 region. Array-CGH analysis shows 10q24.31 (102 832 650-103 511 083) ×3. Our results demonstrate that the pathogenic gene variation of ectrodactyly in this family is due to duplication of 10q24.31 (102 832 650~103 511 083). The haplotype 165-251-289-219-102 can be used as a disease marker for detecting 10q24.31~10q24.32 allele for SHFM.


Assuntos
Duplicação Cromossômica , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Deformidades Congênitas dos Membros/genética , Cromossomos Humanos Par 10/genética , Humanos , Linhagem
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