RESUMO
Bipolar disorder (BD) is commonly comorbid with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). However, little is known about their relationship. This study aimed to assess the impact of comorbid PMS or PMDD on the clinical characteristics of BD. A cross-sectional study was conducted on 262 women with BD. PMS and PMDD were screened with the Premenstrual Symptoms Screening Tool (PSST). Symptomatic features were assessed with Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS), and atypical features by the depressive episode section of SCID-I/P. The rates of PMS and PMDD among BD were 57.6% and 20.6% according to PSST. No significant difference in the rates of PMS and PMDD was found between BD I, BD II, and BD-NOS. Compared to BD patients without PMS or PMDD, patients with comorbid BD and PMS or PMDD were younger, more educated, had a higher risk of OCD, had an earlier age of onset, scored higher on HAMD-17 and its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and were more likely to have increased appetite and leaden paralysis. In addition, patients with comorbid BD and PMDD were less likely to experience traumatic life events, more likely to have family history of mental disorders and have inflammatory or autoimmune disease, scored higher on HMAD-17, particularly in its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and sleep disturbance. Compared with BD without PMS or PMDD, BD with PMS or PMDD might be a specific subtype of BD characterized with earlier onset age, heavier genetic load, increased symptom severity, and atypical features.
Assuntos
Transtorno Bipolar , Transtorno Disfórico Pré-Menstrual , Síndrome Pré-Menstrual , Humanos , Feminino , Transtorno Disfórico Pré-Menstrual/diagnóstico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Estudos Transversais , Síndrome Pré-Menstrual/diagnóstico , Síndrome Pré-Menstrual/epidemiologia , Síndrome Pré-Menstrual/psicologia , China/epidemiologiaRESUMO
BACKGROUND: Sleep fragmentation was shown to be positively associated with cognitive impairment in patients with cerebral small vessel disease (CSVD); however, the underlying mechanisms are not well characterized. In this study, we sought to clarify this issue by investigating the relationship between non breathing-related sleep fragmentation and brain imaging markers in patients with CSVD. METHODS: Eighty-four CSVD patients and 24 age- and sex-matched healthy controls were prospectively recruited. All subjects underwent 3.0 T superconducting magnetic resonance imaging and overnight polysomnography. Polysomnography parameters including sleep onset latency (SOL), total sleep time (TST); sleep efficiency (SE), wake after sleep onset (WASO), percentage of each sleep stage (N1, N2, N3 and rapid eye movement [REM]), arousal index (ArI), periodic limb movement in sleep index (PLSMI), and periodic limb movement related arousal index (PLMAI) were compared between CSVD patients and healthy controls. The relationship between arousal index and CSVD markers was explored in the CSVD group. RESULTS: On polysomnography, CSVD patients showed significantly higher ArI, WASO, PLSMI, and PLMAI, and lower sleep efficiency and N- 3 ratio compared to healthy controls (p < 0.05). On ordinal logistic regression, higher ArI showed a positive association with the severity of periventricular white matter hyperintensity (odds ratio [OR] 1.121, 95% confidence interval [CI] 0.138-2.185) and perivascular space (OR 2.108, 95% CI 1.032-4.017) in CSVD patients, after adjusting for potential confounding variables. CONCLUSIONS: These preliminary results indicate that non breathing-related sleep fragmentation is common and related to the pathological markers of CSVD patients. Future prospective research is required to determine the causal relationship between sleep parameters and CSVD pathology.
Assuntos
Doenças de Pequenos Vasos Cerebrais/complicações , Privação do Sono/complicações , Sono/fisiologia , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Polissonografia , Estudos Prospectivos , Fases do Sono/fisiologia , Substância Branca/fisiopatologiaRESUMO
OBJECTIVE: To analyze (CGG)n repeats sequence and AGG interspersion correlated with unstable expansion of FMR1 gene in a general Chinese population. METHODS: AmplideX FMR1 PCR Kit was used to amplify 380 X chromosomes from randomly selected 176 males and 102 females, 11 permutation carriers and 10 full mutation patients have served as controls. Results of capillary electrophoresis were analyzed with GeneMapper software Version 4.0. SPSS 11.0 software was used for statistical analysis. RESULTS: The ratio of heterozygous females was 64.70%. The number of alleles in general males and females was 15 and 14, the classes of AGG pattern was 26 and 27, respectively. The range of alleles was between 17 to 45 CGG repeats in males and 21 to 44 CGG repeats in females, and 1 male was identified as gray zone carrier. The most frequent allele was 29 CGG repeats, which was followed by 30 and 36 repeats, while 28 CGG repeats were absent. The most common AGG pattern was 9A9A9, 99.21% of the population was detected with different forms and numbers of AGG interruption, and 6A interruption pattern was found in 10.02% samples especially in individuals with more CGG repeats. However, 57.58% of control samples had no AGG interruption, and none of the controls had 6A interruption pattern. No significant difference was observed in allele frequent distribution of (CGG)n repeats and AGG interspersion patterns between the males and females (P > 0.05), and AGGs was significantly different between general population and controls (P < 0.05). CONCLUSION: AGGs and AGG pattern may have important roles in maintaining (CGG)n stability in general population of China, 9A9A6A9 may be a special pattern for preventing (CGG)n unstable expansion in Asian populations.
Assuntos
Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/genética , Repetições de Trinucleotídeos , Adolescente , Adulto , Alelos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: This study aimed to investigate the resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women. METHODS: Total 66 perimenopausal women voluntarily participated in this study from October 2012 to June 2013. Zung Self-rating Depression Scale (ZSDS) was used to assess depression symptoms. Plasma gonadal steroid hormones including estradiol, testosterone, and progesterone were determined by the chemiluminescence immunoassay. A 3.0 Tesla magnetic resonance imaging (MRI) scanner was utilized to acquire resting-state functional MRI data. The z-value functional connectivity map of each participant was calculated voxel-wisely based on the seed region of the hypothalamus. One sample t test of Statistical Parametric Mapping (SPM) were used to determine the brain areas with statistically significant functional connectivity to the hypothalamus, then multiple regression of SPM was used to calculate the correlated areas with 3 gonadal steroid hormones, respectively. Finally, Pearson correlation was performed to analyze bivariate correlations between mean z-values and ZSDS scores. RESULTS: Significant functional connectivity to the hypothalamus were found in brain areas as follows:the lateral inferior frontal gyrus, medial prefrontal cortex, dorsal lateral prefrontal cortex, orbitofrontal cortex, subgenual cortex, anterior cingulate cortex, posterior cingulate cortex, cuneus and precuneus, hippocampus and parahippocampal gyrus, and angular gyrus (False Discovery Rate q<0.05). Among these areas, the plasma testosterone level was positively related to the functional connectivity strength of the right angular gyrus, and negatively related to the strengths of the right subgenual cortex and bilateral medial superior frontal gyrus to the hypothalamus (PAlphaSim<0.05). Especially, mean z-value in the subgenual cortex was positively related to the ZSDS index score (r=0.279, P=0.023), and factor scores of the core depression symptoms (r=0.278, P=0.024) and somatic symptoms (r=0.357, P=0.003). CONCLUSION: In perimenopausal women, the hypothalamus has resting-state functional connectivity with widespread areas involved in the brain depression-related network and default mode network, and the plasma androgen level may modulate the functional connectivity strengths of the hypothalamus and decrease the susceptibility of perimenopausal women to depression.
Assuntos
Depressão , Transtorno Depressivo , Perimenopausa , Encéfalo , Mapeamento Encefálico , Feminino , Hormônios Esteroides Gonadais , Humanos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Subsyndromal depression (SSD) is considered as a predictor for future depressive disorders, however whether white matter abnormalities are involved in the high-susceptibility of women to depressive disorders during perimenopause is unknown. The purpose of this study was to investigate fractional anisotropy (FA) in the white matter of the whole brain in perimenopausal women with SSD using diffusion tensor imaging (DTI). METHODS: In a cross-sectional study, 24 perimenopausal women with SSD and 24 other age-, education-, and body mass index-matched healthy women underwent DTI. A voxel-based analysis was used to elucidate regional FA changes at a voxel threshold of p < 0.001 with an extent threshold of k > 127 voxels (p < 0.05, AlphaSim correction). Subsequently, correlation analyses were performed between mean FA values in significant brain regions and plasma estradiol level. RESULTS: Compared to healthy controls, women with SSD exhibited significantly lower FA values in the left insula, while higher FA values were observed in the left ventral lateral thalamus and left and right brainstem in the midbrain. In subjects with SSD, the mean FA value in the left insula was positively correlated to plasma estradiol levels (r = 0.453, p = 0.026) (uncorrected). CONCLUSIONS: Our findings indicate altered microstructures in white matter of the insula and subcortical regions may be associated with the high susceptibility of perimenopausal women to depressive disorders. Estrogen may modulate the white matter microstructure of the insula.
Assuntos
Transtorno Depressivo/patologia , Perimenopausa/fisiologia , Substância Branca/patologia , Anisotropia , Tronco Encefálico/patologia , Estudos de Casos e Controles , Córtex Cerebral/patologia , Estudos Transversais , Imagem de Tensor de Difusão/métodos , Estradiol/metabolismo , Feminino , Humanos , Mesencéfalo/patologia , Pessoa de Meia-Idade , Núcleos Ventrais do Tálamo/patologiaRESUMO
We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously been implicated in the pathogenesis of polyglutamine expansion diseases. Our findings link this gene to XLMR and shed more light on the pathogenesis of this common disorder.
Assuntos
Deficiência Intelectual Ligada ao Cromossomo X/genética , Mutação/genética , Oligopeptídeos/genética , Proteínas de Transporte/genética , Proteínas de Ligação a DNA , Feminino , Ligação Genética , Humanos , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/classificação , Deficiência Intelectual Ligada ao Cromossomo X/etiologia , Dados de Sequência Molecular , Proteínas Nucleares/genética , Linhagem , SíndromeRESUMO
OBJECTIVE: To determine genetic cause for a patient with development delay and multiple congenital anomalies. METHODS: Routine karyotype analysis was performed for the patient and his parents. Array comparative genomic hybridization (array CGH) was performed for the patient to detect cryptic chromosome aberration. RESULTS: Karyotype analysis revealed no obvious anomaly for the patient and his parents. Array CGH has detected a 2.8 Mb heterozygous deletion at 9q34.3 and an 8.1 Mb heterozygous duplication at 22q. Fluorescence in situ hybridization analysis of the patient revealed an unbalanced subtelomeric translocation 46, XY, der(9) t(9; 22) (q34.3; q13.2q13.33) mat, which has resulted in partial trisomy 22q and partial monosomy 9q. Clinical features of the patient included developmental delay, facial dysmorphism and multiple congenital anomalies. Upon subsequent pregnancy, FISH analysis revealed that the fetus has inherited the normal chromosomes 9 and 22 from his mother. Postnatal follow-up confirmed normal development milestone and physiques in the child. CONCLUSION: An unbalanced translocation involving 9q and 22q has been found in a child featuring multiple congenital anomalies, which is due to a balanced translocation 9; 22 in his mother. Array CGH and FISH have also helped with discovery of subtelomeric rearrangement. Prenatal diagnosis of this aberration in subsequent pregnancies with FISH can prevent the recurrence of this disease.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 9 , Deficiência Intelectual/genética , Translocação Genética , Feminino , Humanos , Lactente , MasculinoRESUMO
OBJECTIVE: To develop a screening program for spinal muscular atrophy (SMA) carriers, and to assess the carrier frequency and detection rate in Shanghai region. METHODS: Quantitative analysis of the SMN1 gene by real-time PCR was developed using specimens from 15 SMA patients and 76 SMA parents from 38 affected nuclear families. A pilot screening was carried out for 1741 asymptomatic pregnant women. Frequencies of SMN1 alleles were determined with the Hardy-Weinberg equilibrium. RESULTS: Forty five out of the 1741 women were identified as SMA carriers by the presence of single copy of SMN1. The frequencies of no copy, 1 copy, 2 copy and 3 copy alleles were 1.37 U+00D7 10-2, 9.45 U+00D7 10-1, 2.80 U+00D7 10-2 and 1.27 U+00D7 10-2, respectively. The adjusted SMA carrier frequency was 1:35 with a detection rate of 94.49%. For those with a negative screening result, individuals with 3 copies carried a higher residual risk. CONCLUSION: The incidence of SMA carriers in Shanghai region is similar with that in Caucasian populations. Carrier screening has high detection efficiency. An effort should be made to further distinguish SMN1 gene copy numbers for those with more than 2 copies, since accurate determination of 2 and 3 copy allele frequencies is essential for post-screening genetic consulting.
Assuntos
Heterozigoto , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Alelos , Feminino , Dosagem de Genes , Frequência do Gene , Humanos , Masculino , Projetos Piloto , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Proteína 1 de Sobrevivência do Neurônio Motor/genéticaRESUMO
OBJECTIVE: Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers. DESIGN: Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated. RESULTS: 22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2-amplified gastric cancers. CONCLUSION: The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies.
Assuntos
Amplificação de Genes , Deleção de Genes , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Antineoplásicos/uso terapêutico , Receptores ErbB/genética , Marcadores Genéticos , Terapia de Alvo Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas p21(ras) , Receptor ErbB-2/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Proteínas ras/genéticaRESUMO
Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-kappaB, and Wnt/beta-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms.
Assuntos
Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To characterize molecular and cytogenetic abnormalities in six 46, XX males, and to investigate the clinical manifestations and underlying mechanisms in such patients. METHODS: Clinical data of six XX male patients were collected. Karyotyping, multiple polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) were utilized to detect and locate the sex determining region (SRY) gene. RESULTS: PCR and FISH showed that all patients were SRY-positive XX males. All patients have their SRY gene located at the tip of derivative X chromosomes, which have resulted from translocation between short arms of X and Y chromosomes. High resolution karyotyping at 550-750 band level has revealed that the translocation breakpoints were at Xp22.33 and Yp11.2 in three patients. In the remaining patients, the breakpoints were either at Xp22.32 and Yp11.31 or Xp22.31 and Yp11.2. The breakpoints at Xp22.32, Xp22.31 and Yp11.31 were rarely reported. Genotype-phenotype correlation analysis indicated that the clinical manifestations were age-specific. Four adult patients have come to clinical attention due to infertility, with typical features including azoospermia and testis dysgenesis, whereas poorly developed secondary sexual characteristics and short stature were main complaints of adolescence patients, and short stature was the sole symptom in a child patient. CONCLUSION: Combined karyotyping, PCR and FISH are important for the analysis of XX males. Particularly, high resolution karyotyping is valuable for the refinement of chromosome breakpoints and detailed analysis of genotype-phenotype correlation.
Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Cromossomos Humanos X , Cromossomos Humanos Y , Aberrações dos Cromossomos Sexuais , Translocação Genética , Adolescente , Adulto , Pré-Escolar , Estudos de Associação Genética/métodos , Humanos , Cariotipagem/métodos , Masculino , Adulto JovemRESUMO
Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.
Assuntos
Córtex Cerebral/metabolismo , Dendritos/metabolismo , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Western Blotting , Linhagem Celular , Forma Celular/fisiologia , Células Cultivadas , Córtex Cerebral/citologia , Feminino , Humanos , Neurônios/citologia , Fosforilação/fisiologia , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , Ratos , Ratos Sprague-Dawley , Proteínas rac1 de Ligação ao GTP/genéticaRESUMO
Graves' disease (GD) is one of the most common human autoimmune diseases, and recent data estimated a prevalence of clinical hyperthyroidism of 0.25-1.09% in the population. Several reports have linked GD to the region 5q12-q33; and a locus between markers D5s436 and D5s434 was specifically linked to GD susceptibility in the Chinese population. In the present study, association analysis was performed using a large number of single-nucleotide polymorphisms (SNPs) at this locus in 2811 patients with GD recruited from different geographic regions of China. The strongest associations with GD in the combined Chinese Han cohorts were mapped to two SNPs in the promoter (pSNP) of SCGB3A2 [SNP76, rs1368408, P = 1.43 x 10(-6), odds ratio (OR) = 1.28 and SNP75, -623 - -622, P = 7.62 x 10(-5), OR = 1.32, respectively], a gene implicated in immune regulation. On the other hand, pSNP haplotypes composed of the SNP76 (rs1368408)+SNP74 (rs6882292) or SNP76+SNP75 (-623 approximately -622, AG/T) variants are correlated with high disease susceptibility (P = 0.0007, and P = 0.0192, respectively) in this combined Chinese Han cohort. Furthermore, these haplotypes were associated with reduced SCGB3A2 gene expression levels in human thyroid tissue, while functional analysis revealed a relatively low efficiency of SCGB3A2 promoters of the SNP76+SNP75 and SNP76+SNP74 haplotypes in driving gene expression. These results suggest that the SCGB3A2 gene may contribute to GD susceptibility.
Assuntos
Predisposição Genética para Doença , Doença de Graves/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas , Proteínas/genética , Uteroglobina/genética , Animais , Pareamento de Bases/genética , Sequência de Bases , Sítios de Ligação , Sequência Conservada , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ligação Genética , Marcadores Genéticos , Haplótipos , Humanos , Camundongos , Dados de Sequência Molecular , Proteínas/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Análise de Regressão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Secretoglobinas , Uteroglobina/metabolismoAssuntos
Aorta Torácica/anormalidades , Cardiopatias Congênitas/genética , Ventrículos do Coração/anormalidades , RNA não Traduzido/genética , Síndrome de Wolf-Hirschhorn/genética , Feminino , Feto , Estudos de Associação Genética , Cardiopatias Congênitas/etiologia , Humanos , Gravidez , Estenose da Valva Pulmonar , Reação em Cadeia da Polimerase em Tempo Real , Síndrome de Wolf-Hirschhorn/complicaçõesRESUMO
OBJECTIVE: To determine the origin of aberrant chromosomes involving the short arm of chromosome 8 in two mentally retarded children, and to correlate the karyotype with abnormal phenotype. METHODS: Routine G-banding was performed to analyze the karyotypes of the two patients and their parents, and array comparative genomic hybridization (array CGH) was used for the first patient for fine mapping of the aberrant region. RESULTS: The first patient presented with only mental retardation. The father had normal karyotype. The mother had an apparent insertion translocation involving chromosomes 8 and 3 [46, XX, inv ins (3; 8) (q25.3; p23.1p11.2)], the karyotype of the child was ascertained as 46, XX, der(3) inv ins (3; 8)(q25.3; p23.1p11.2). Array CGH finely mapped the duplication to 8p11.21-8p22, a 26.9 Mb region. The other patient presented with mental retardation, craniofacial defects, congenital heart disease and minor skeletal abnormality. The mother had normal karyotype. The father had an apparently balanced translocation involving chromosome 8p and 11q, the karyotype was 46, XY, t(8; 11)(p11.2; q25). The karyotype of the child was then ascertained as 46, XX, der(11)t(8; 11)(p11.2; q25). CONCLUSION: These results suggested that partial trisomy 8p was primary cause for the phenotypic abnormalities of the two patients, whereas a mild phenotypic effect was observed in patient 1. Parental karyotype analysis could help define the aberrant type and recurrent risk evaluation. In contract to routine karyotype analysis, aberrant regions could be mapped by array CGH with higher resolution and accuracy.
Assuntos
Translocação Genética , Trissomia/genética , Trissomia/patologia , Pré-Escolar , Cromossomos Humanos Par 8/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Deficiência Intelectual/etiologia , Deficiência Intelectual/genética , Cariotipagem , Masculino , FenótipoRESUMO
OBJECTIVE: To determine the origin of chromosomal aberrants in a mentally retarded children, and to correlate the karyotype with phenotype. METHODS: Routine G-banding were performed to analyze the karyotype of the patient and her parents, and array comparative genomic hybridization (array CGH) were used for finely mapping the aberrant regions. RESULTS: The mother had a normal karyotype. The father had an apparently balanced translocation involving chromosome 7q and 14q, the karyotype was 46, XX, t(7;14) (q34;q32), the karyotype of the child was then ascertained as 46, XX, der(14) t(7;14) (q34;q32.33) pat. Array CGH finely mapped the duplication to 7q34-qter, a 17.09 Mb region, and a very small associated deletion of distal chromosome 14 to 14q32.33-qter, a 2.27 Mb region. The patient presented some frequently seen features in partial trisomy 7q cases such as mental retardation, low birth weight, small nose, cleft palate, low-set ears and short neck. CONCLUSION: This result suggested that partial trisomy 7q exert mainly phenotypic effect on the patient. Parental karyotype analysis could help define the aberrant type.
Assuntos
Cromossomos Humanos Par 14 , Cromossomos Humanos Par 7 , Translocação Genética , Trissomia/genética , Anormalidades Múltiplas/genética , Adulto , Pré-Escolar , Bandeamento Cromossômico , Cromossomos Humanos Par 7/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , MasculinoRESUMO
OBJECTIVE: To develop an efficient, high resolution PCR assay suitable for detection of the (CGG)n repeats of the fragile X mental retardation 1 (FMR1) gene by optimizing the PCR system in combination with capillary electrophoresis. METHODS: Three standard samples and twelve samples that were verified by Southern blot analysis including both male and female in the normal, pre- and full mutation range were used in this study to evaluate the enhanced PCR system. All amplicons were electrophoresed by agarose, polyacrylamide and capillary electrophoresis to compare the results. RESULTS: The enhanced PCR assay developed in this study was able to detect a full mutation with (CGG)n being larger than 260 repeats in a male. An expanded pre-mutation allele with (CGG)n as large as 183 repeats in a female was also amplified. The capillary electrophoresis method used in this study was able to distinguish two alleles with 1 CGG repeat difference and the results were reproducible. CONCLUSION: A high resolution PCR assay is developed, which is much more efficient than the general PCR systems. It is suitable for the clinical screening of FMR1 gene and will greatly reduce the number of Southern blot analysis needed in clinical application.
Assuntos
Análise Mutacional de DNA/métodos , Eletroforese Capilar/métodos , Proteína do X Frágil da Deficiência Intelectual/genética , Mutação , Reação em Cadeia da Polimerase/métodos , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: To clarify advantages and disadvantages of using multiplex ligation-dependent probe amplification (MLPA) for detecting exonic deletions and duplications of the Dystrophin gene, and to explore the appropriate management for single-exon abnormality detected by MLPA. METHODS: MLPA were performed to detect exonic copy number changes in 70 Duchenne/Becker muscular dystrophy (DMD/BMD) patients diagnosed by clinical and histological findings. PCR, DNA sequencing and real-time PCR were applied to the samples in which MLPA indicated single-exon deletion or duplication. RESULTS: Of all 70 patients, MLPA detected exonic deletions in 42 (60%), including 12 with single-exon deletion and one with ambiguous single-exon deletion. Exon duplications were found in 7 patients (10%), among which two were single-exon duplication. 21 patients showed normal results (30%). For the 12 patients with single-exon deletion, MLPA results were confirmed by PCR in 11. In one patient, a deletion of two nucleotides (c.4470-4471delAA) was found by sequencing. A novel two-nucleotide deletion (c.4746-4747delCT) was identified in the patient with the ambiguous single-exon deletion. For the two patients showed single-exon duplication, MLPA results were confirmed by real-time PCR. CONCLUSION: MLPA should be the first choice in detecting Dystrophin gene exon deletions and duplications. Single-exon deletion/duplication resulted from MLPA should be further evaluated by other methods.
Assuntos
Variações do Número de Cópias de DNA , Distrofina/genética , Éxons , Técnicas de Amplificação de Ácido Nucleico/métodos , Sequência de Bases , Análise Mutacional de DNA , Deleção de Genes , Duplicação Gênica , HumanosRESUMO
In this paper, we propose a parallel and scalable approach for geodesic distance computation on triangle meshes. Our key observation is that the recovery of geodesic distance with the heat method [1] can be reformulated as optimization of its gradients subject to integrability, which can be solved using an efficient first-order method that requires no linear system solving and converges quickly. Afterward, the geodesic distance is efficiently recovered by parallel integration of the optimized gradients in breadth-first order. Moreover, we employ a similar breadth-first strategy to derive a parallel Gauss-Seidel solver for the diffusion step in the heat method. To further lower the memory consumption from gradient optimization on faces, we also propose a formulation that optimizes the projected gradients on edges, which reduces the memory footprint by about 50 percent. Our approach is trivially parallelizable, with a low memory footprint that grows linearly with respect to the model size. This makes it particularly suitable for handling large models. Experimental results show that it can efficiently compute geodesic distance on meshes with more than 200 million vertices on a desktop PC with 128 GB RAM, outperforming the original heat method and other state-of-the-art geodesic distance solvers.
RESUMO
OBJECTIVES: To survey anxiety and depression symptoms to COVID-19 outbreak in the public, medical staff and patients during the initial phase of the pandemic. DESIGN: Cross-sectional online survey administered through WeChat Mini Program using Chinese versions of Zung Self-rating Depression Scale and Zung Self-rating Anxiety Scale. SETTING: Guangzhou, China. PARTICIPANTS: 47 378 public, 1512 medical staff and 125 patients with COVID-19. RESULTS: Higher rates of depression (47.8%) and anxiety symptoms (48.7%) were shown by patients who were screened positive compared with those of the public (35.6%, 25.7%) or medical staff (15.4%, 13.3%). The professional identity of a nurse, conditions of 'with an infected family member' and 'working at the frontline' were risk factors to depression or anxiety symptoms for the medical staff. Younger age, lower educational level, female and not having adequate masks were the risk factors for the public. CONCLUSION: The COVID-19 outbreak increased people's depression or anxiety emotion responses, which varied extensively among the patients, public and medical staff.