Correlation In Chinese Patients Research Articles

Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with gilbert and crigler-Najjar II syndrome

The spectrum of UDP-glucuronosyltransferase (UGT1A1) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual UGT1A1 variants in GS and CNS-II remains to be clarified. To explore the UGT1A1 variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected for screening variants in the gene UGT1A1 by a polymerase chain reaction and Sanger sequencing. The correlation between different UGT1A1 variants and clinical phenotypes was analyzed. A total of 21 UGT1A1 variants were identified, including nine novel variants, and constituted 42 UGT1A1 genotypes in the GS and CNS-II patients. The most common UGT1A1 variants were A (TA)7TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A (TA)7TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of UGT1A1, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A (TA)7TAA, homozygous p.G71R, compound heterozygous A (TA)7TAA/p.G71R and A (TA)7TAA/p.P364L, and combined heterozygous A (TA)7TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A (TA)7TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A (TA)7TAA/p.G71R, single heterozygous A (TA)7TAA, single heterozygous p.G71R, and homozygous A (TA)7TAA. The spectrum of UGT1A1 genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of UGT1A1.

Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis

ObjectiveThis study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS).MethodsRetrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years).ResultsA total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences.ConclusionThis study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.

Sex differences in subjective cognitive impairment and clinical correlates in Chinese patients with subthreshold depression

ObjectiveSubthreshold depression (SD) is a global mental health problem given its high prevalence, comorbidity, functional impairment, and its association with increased service utilization. However, currently little is known about sex differences of SD in cognitive impairment with clinical correlates. This study aims to explore sex differences in subjective cognitive impairment and clinically associated risk factors in Chinese patients with subthreshold depression (SD).MethodsA total of 126 patients with SD, 40 males and 86 females, aged 18–45 years, were included in this cross-sectional observational study. Their general information, psychological assessments, and psychiatric symptom assessments were collected online. The Patient Health Questionnaire depression-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Perceived Deficits Questionnaire-Depression (PDQ-D), and Toronto Alexithymia Scale (TAS-20) with 3 subdomains were used. The obtained scores were analyzed with partial correlation and multiple linear regression analysis models.ResultsOur results showed that females had significantly higher PDQ-D-20 total score than males. However, the differences in TAS-20 and subdomain score according to sex were not significant. Notably, TAS-20 and DDF (difficulty describing feelings) subdomain contributed to cognitive impairment in males, whereas both PHQ-9 total score and TAS-20 or DDF subdomain contributed to cognitive impairment in females.ConclusionThese findings revealed significant sex differences in cognitive impairment and clinical correlates in SD, which should be further followed-up in the future.

Heterogeneity of Axenfeld-Rieger Syndrome: Molecular and Clinical Findings in Chinese Patients.

Axenfeld–Rieger Syndrome (ARS) is a rare disease with a wide spectrum of ocular and systemic manifestations. The genetic spectrum of Chinese patients with ARS and genotype-phenotype correlations have yet to be described. To explore the molecular and clinical features in Chinese patients, fifty-five patients clinically diagnosed with ARS from independent families were recruited. Complete ophthalmic examinations and next generation sequencing of anterior segment dysgenesis associated genes were performed in all patients, and segregation in available relatives was verified using Sanger sequencing. 18 FOXC1 variants, 13 PITX2 variants, and two gross deletions spanning FOXC1 were detected in 35 out of 55 (63.6%) patients. 12 FOXC1 variants, 9 PITX2 variants, and two gross deletions were novel. There was a wide range of variability and severity in ocular and systemic manifestations displayed in our patients. Patients with FOXC1 variants were diagnosed at a younger age and had a lower prevalence of systemic manifestations than patients harboring PITX2 variants and those without variants. To our best knowledge, this is the largest study of Chinese patients with ARS to date. Our findings expand the genetic spectrum of ARS and reveal genotype-phenotype correlations in Chinese patients with ARS. Genetic and clinical heterogeneity were present in our patients. Awareness of the extensive characterization may aid in the clinical management and genetic counseling of patients with this rare disease.

Mutation analysis of the ATP7B gene and genotype\u2013phenotype correlation in Chinese patients with Wilson disease

AimTo discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype–phenotype correlation in a large-scale sample of Chinese WD patients.MethodsOne hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Direct sequencing of all 21 exons within ATP7B was performed. Subsequently, an extensive study of the overall spectrum and frequency of ATP7B mutations and genotype–phenotype correlation was performed in all Chinese patients eligible from the literature, combined with the current southern group.ResultsIn 103 patients with WD, we identified 48 different mutations (42 missense mutations, 4 nonsense mutations and 2 frameshifts). Of these, 3 mutations had not been previously reported: c.1510_1511insA, c.2233C>A (p.Leu745Met) and c.3824T>C (p.Leu1275Ser). The c.2333G>T (p.Arg778 Leu) at exon 8, was the most common mutation with an allelic frequency of 18.8%, followed by c.2975C>T (p.Pro992Leu) at exon 13, with an allelic frequency of 13.4%. In the comprehensive study, 233 distinct mutations were identified, including 154 missense mutations, 23 nonsense mutations and 56 frameshifts. Eighty-five variants were identified as novel mutations. The c.2333G>T (p.Arg778 Leu) and c.2975C>T (p.Pro992Leu) were the most common mutations, with allelic frequencies of 28.6% and 13.0%, respectively. Exons 8, 12, 13, 16 and 18 were recognised as hotspot exons. Phenotype–genotype correlation analysis suggested that c.2333G>T (p.Arg778 Leu) was significantly associated with lower levels of serum ceruloplasmin (P = 0.034). c.2975C>T (p.Pro992Leu) was correlated with earlier age of disease onset (P = 0.002). Additionally, we found that the c.3809A>G (p.Asn1270Ser) mutation significantly indicated younger onset age (P = 0.012), and the c.3884C>T (p.Ala1295Val) mutation at exon 18 was significantly associated with hepatic presentation (P = 0.048). Moreover, the patients with mixed presentation displayed the initial WD features at an older onset age than the groups with either liver disease or neurological presentation (P = 0.039, P = 0.015, respectively). No significant difference was observed in the presence of KF rings among the three groups with different clinical manifestations.ConclusionIn this study, we identified three novel mutations in 103 WD patients from the southern part of China, which could enrich the previously established mutational spectrum of the ATP7B gene. Moreover, we tapped into a large-scale study of a Chinese WD cohort to characterise the overall phenotypic and genotypic spectra and assess the association between genotype and phenotype, which enhances the current knowledge about the population genetics of WD in China.

Psychological stress and its correlates in Chinese patients with acute coronary syndrome

Abstract Funding Acknowledgements None. Background Psychological stress is associated with high incidence of coronary heart disease and increases the risk of mortality and poor health status. Although a few studies have investigated psychological stress in this population, this problem is usually unrecognized and untreated in most Chinese patients with acute coronary syndrome. There is insufficient information regarding the features of psychological stress and associated factors among this population. Purpose This study aimed to assess the level of psychological stress and to identify its correlates in Chinese patients with acute coronary syndrome. Methods Patients aged over 18 years and with acute coronary syndrome were invited to participate in a cross-sectional survey in two tertiary public hospitals in China, from June to July 2019. A total of 332 patients completed measures of sociodemographic and clinical characteristics, psychological stress (10-item Perceived Stress Scale), and illness perception (Brief Illness Perceptions Questionnaire). Independent sample t-tests, bivariate correlations, and multivariable linear regression were performed to analyze potential correlates, including age, gender, education level, employment status, income, episode of illness, revascularization procedure, comorbidities, body mass index, blood pressure, blood glucose, blood lipids, and illness perception. Results The average patient age was 62.2 years, 67.5% were male, and 54.2% had less than high school education. The mean score for psychological stress was 21.30 ± 3.99 and 66.9% of patients had high psychological stress (score ≥ 20). Multivariable regression analysis showed that being overweight/obesity versus normal weight (body mass index: ≥ 24 kg/m2 versus &amp;lt; 24 kg/m2) was associated with lower psychological stress (β = -0.134, p = 0.007). Having a high level of fasting blood glucose (≥ 6.1 mmol/L) versus normal fasting blood glucose (&amp;lt; 6.1 mmol/L) was associated with high psychological stress (β = 0.123, p = 0.017). Additionally, negative cognitive illness perception (β = 0.190, p = 0.01), negative emotional illness perception (β = 0.290, p &amp;lt; 0.001), and poor illness understanding (β = 0.118, p = 0.032) were associated with high psychological stress. Conclusions Patients with acute coronary syndrome experience high psychological stress that is significantly correlated with body mass index, fasting blood glucose, and illness perception. Health professionals should recognize this issue and interventions looking to relive psychological stress may benefit from targeting these correlates.

Sex differences in association between cognitive impairment and clinical correlates in Chinese patients with first-episode drug-na\xefve schizophrenia

BackgroundSchizophrenia is a complex mental illness with significant sex differences. Cognitive impairment is common in patients with schizophrenia, even in remission. This study was designed to examine the sex differences in the relationship between cognitive impairment and clinical correlations with first-episode drug-naïve (FEDN) schizophrenia.Methods93 FEDN patients (male/female = 45/48) and 160 controls (male/female = 74/86) were enrolled to compare the sex differences in cognitive functions measured by the MATRICS Consensus Cognitive Battery (MCCB). Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Scale (HAMD) were used to evaluate patients' clinical symptoms. We compared cognitive impairment with sociodemographic characteristics and measures of different genders, as well as group-by-sex interactions.ResultsOur results showed that male patients had significantly lower scores for symbol coding, digital sequence, and verbal learning than female patients, while the healthy controls showed similar sex differences. In female patients, multiple linear regression analysis confirmed that PANSS negative symptoms and general psychopathology scores, HAMD total score, and education level were independent contributors to MCCB total score. In male patients, only education was an independent contributor to MCCB total score.ConclusionsThese findings revealed significant sex differences in cognitive impairments and clinical symptoms in FEDN, which will be worthy of a follow-up study of schizophrenia in the future.

Identification of the genetic basis of sporadic polydactyly in China by targeted sequencing

PurposePolydactyly is a highly heterogeneous group of skeletal deformities in clinical and genetic background. The variation spectrum in Chinese sporadic polydactyly has not been comprehensively analyzed. To elucidate genetic variation spectrum and genotype-phenotype correlations in Chinese patients with polydactyly, we conducted comprehensive genetic analysis of patients nationwide using targeted sequencing. MethodsA total of 181 patients diagnosed with polydactylies were recruited. We designed a targeted capture panel for sequencing 721 genes that are associated with the pathogenesis of skeletal dysplasia. We performed rigorous variant- and gene-level filtrations to identify potentially damaging variants, followed by enrichment analysis and gene prioritization. ResultsA total of 568 deleterious variants of 293 genes were identified in 173 of 181 patients with a positive rate of 95.6% by targeted sequencing. For each sample, an average of 3.17 deleterious variants were identified. Especially, 14 pathogenic or likely pathogenic variants were identified in 10 genes in 14 patients out of the 181 patients, providing a positive molecular diagnostic rate of 7.7%. ConclusionTargeted sequencing analysis provides a high efficiency approach for the genetic diagnosis of polydactyly. This is the largest next generation sequencing study performed to date in patients with polydactyly and represents the genetic basis of polydactyly typically encountered in genetics clinics.

Gene mutations associated with early onset familial Alzheimer's disease in China: An overview and current status.

BackgroundMutations of three causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early‐onset familial Alzheimer's disease (EOFAD). The prevalence of causative gene mutations in patients with EOFAD has been reported in previous studies worldwide but remains unclear in China. The patients with these known mutations always show considerable clinical phenotypic variability. However, to date, there have been no detailed descriptions of the clinical phenotypes associated with these Chinese EOFAD mutations. Thus, the aim of this study was to describe all of the known mutations in three EOFAD causative genes and genotype–phenotype correlations in Chinese patients with EOFAD.MethodWe systematically searched the PubMed, MEDLINE, CNKI, VIP, and WAN‐FANG databases to find Chinese EOFAD mutations in reports from inception through May 2020.ResultWe identified 31 studies reporting mutations of three causative genes in China. 10 mutations in APP gene, 27 mutations in PSEN1 gene and six mutations in PSEN2 were discovered in Chinese EOFAD. This review summarized all these probably pathogenic mutations as well as its clinical features. To the best of our knowledge, this is the first systemic review of causative gene mutations in patients with EOFAD in China.ConclusionThe analysis of the genetic and clinical phenotype correlations in this review supports the idea that the clinical phenotype might be influenced by specific genetic defects. It also suggests genetic testing and genotype–phenotype correlations are important for the accurate diagnosis and for understanding disease‐associated pathways and might also improve disease therapy and prevention.

Poor Insight in Schizophrenia Patients in China: a Meta-Analysis of Observational Studies.

Poor insight exists in all phases of schizophrenia and is associated with poor clinical prognosis and adverse psychosocial functioning. This is a meta-analysis examining the prevalence of poor insight and its correlates in Chinese patients with schizophrenia. Both major international (PubMed, EMBASE, PsycINFO, and Web of Science) and Chinese (WANFANG and CNKI) databases were systematically searched. The pooled prevalence of poor insight was calculated using the random-effects model. A total of 19 studies with 3112 schizophrenia patients were included. The prevalence of poor insight was 43.4% (95%CI: 36.0%-51.2%). Subgroup and meta-regression analyses revealed that the higher prevalence of poor insight was significantly associated with single-site design, smaller sample size, inpatient status, acute illness phase, higher male proportion, younger age, shorter duration of illness, lower study quality, and earlier publication year. Poor insight is common in Chinese schizophrenia patients. Considering the negative outcomes of poor insight, regular screening and effective psychosocial interventions should be delivered for this vulnerable population.

Genotypes and Phenotypes of DMD Small Mutations in Chinese Patients With Dystrophinopathies.

Dystrophinopathies are a group of neuromuscular disorders resulting from mutations in DMD, including Duchenne muscular dystrophy (DMD), intermediate muscular dystrophy (IMD), and Becker muscular dystrophy (BMD). Herein, we present the characteristics of small mutations in Chinese patients with dystrophinopathies, and explore genotype–phenotype correlations. In our cohort, 115 patients with small mutations (18.49% of all patients) were included and DMD mutations were detected by either Sanger (53.91%) or next generation sequencing (46.09%). In total, 106 small mutations were detected, 28 of which (26.42%) had not been reported previously. The most common mutations were nonsense mutations (52.17%), followed by splicing (24.35%), frameshift (17.39%), and missense mutations (5.22%), in addition to a single untranslated region mutation (0.87%). We discovered distinct mutation characteristics in our patients, such as different positional distributions, indicating different exon skipping therapy strategies for small mutations in Chinese patients. Almost all patients (96.51%) with truncating or missense mutations, were covered by triple/double/single-exon skipping therapy; the most frequent single-exon skipping strategy was skipping exon 32, applicable for 8.51% of patients. Furthermore, splicing classification grades were correlated with phenotypes in nonsense mutations (P < 0.001), and serum creatinine levels differed significantly between DMD/IMD and BMD for patients ≤ 16 years old (P = 0.002). These observations can further aid prognostic judgment and guide treatment. In conclusion, the mutation characteristics and genotype–phenotype correlations in Chinese patients with dystrophinopathies and small mutations could provide insights into the molecular mechanisms of pathogenesis, diagnosis, and treatment designs.

Prevalence, risk factors and clinical characteristics of osteoporosis in Chinese inpatients with schizophrenia

Patients with schizophrenia have a high prevalence of developing osteoporosis and osteoporosis-related fractures. We examined the prevalence of osteoporosis and its clinical correlates in Chinese patients with schizophrenia, which is not well-studied. A total of 199 inpatients (males/females=132/67; average age: 54.5±11.1years) and 107 healthy controls (males/females=22/85; average age: 41.7±11.9years) were recruited. Bone mineral density (BMD) was measured by ultrasonography of the calcaneus. The prevalence of osteoporosis and low BMD (osteoporosis and osteopenia) was 23.1% and 65.3% for the patient group, versus 7.5% and 39.3% for the control group (both p<0.001). Further, the average BMD T-score in patients was significantly lower than in controls (p<0.05). There was gender difference in the prevalence of low BMD conditions for the patients (males: 56.1% versus females: 76.1%; p<0.01) as well as the BMD T-score (p<0.001). Several risk factors correlated with the osteoporosis classification in the patient group: older age (58.9±11.2years vs. 53.3±11.0years), lower weight (63.7±12.2kg vs. 70.4±15.2kg) and body mass index (BMI) (22.8±4.1kg/m2 vs. 24.2±4.7kg/m2; all p<0.01) than those without osteoporosis. Stepwise multiple logistic regression analysis indicated that age, weight and BMI remained significantly associated with osteoporosis. In addition, correlation analysis showed significant correlations between BMD T-score and the following parameters: gender, age and drug type (clozapine versus non-clozapine) (Bonferroni corrected p's<0.05). Our results suggest a higher prevalence of osteoporosis and osteopenia in Chinese schizophrenic inpatients, with both the expected risk factors of gender and age, as well as drug type.

The molecular heterogeneity of sporadic colorectal cancer with different tumor sites in Chinese patients.

PurposeTo assess the biological variability of clinical meaningful molecular markers and their clinical correlations in Chinese patients with colorectal cancer (CRC).Materials and methodsIn this prospective observational study, frequencies and clinico-pathological features of RAS and BRAFV600E mutations, deficiency of DNA mismatch repair (dMMR) were evaluated in patients with colorectal cancer staged I-IV. The molecular heterogeneity between right-sided and left-sided colorectal cancers was studied in our series by classifying patients with different mutations and dMMR status.ResultsAmong 400 evaluable patients, mutations in KRAS exon 2, exon 3 or 4, NRAS and BRAFV600E were detected in 36%, 7.5%, 3.5% and 2.5%, respectively. RAS mutations were significantly higher in metastatic CRCs (56.4% vs. 43.1%, p=0.015) and right-sided CRCs (62.5% vs 41.7%, p=0.003). In 212 RAS wild-type patients, V600E mutation was higher in older patients (9.5% vs. 2.2%, p=0.017), women (9.2% vs. 2.2%, p=0.021) and right-sided CRCs (10.5% vs. 3.4%, p=0.06). dMMR was detected in 7.75% of all stages of CRCs, with the highest dMMR rate of 40% in stage II right-sided colon cancer.ConclusionsBy assessing the mutations and clinical correlations of RAS and BRAF genes, and dMMR status, similar RAS mutation, dMMR frequency and lower BRAF mutation was observed in Chinese patients compared to western patients. A distinct molecular heterogeneity was found between patients with right-sided and left-sided CRCs.

Genotype-phenotype correlation in Chinese patients with spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disease characterized by slowly progressive weakness and atrophy of proximal limbs and bulbar muscles. To assess the genotype-phenotype correlation in Chinese patients, we identified 155 patients with SBMA and retrospectively examined available data from laboratory tests and neurophysiological analyses. Correlations between genotype and phenotype were analyzed. There was an inverse correlation between the length of CAG repeats and age at first muscle weakness (p<0.0001). The serum creatine kinase level showed a significant inverse correlation with disease duration and the age at examination (p=0.019 and p=0.004, respectively). Unlike previous classification of motor- and sensory-dominant phenotypes, all findings of nerve conduction, except the amplitudes of median nerve compound motor action potential, were positively correlated to the length of CAG repeats. A significant decline in sensory nerve action potential amplitudes may assist differential diagnosis of SBMA.

Clinical features and gene mutational spectrum of CDKL5-related diseases in a cohort of Chinese patients

BackgroundMutations in the cyclin-dependent kinase-like 5 (CDKL5) (NM_003159.2) gene have been associated with early-onset epileptic encephalopathies or Hanefeld variants of RTT(Rett syndrome). In order to clarify the CDKL5 genotype-phenotype correlations in Chinese patients, CDKL5 mutational screening in cases with early-onset epileptic encephalopathies and RTT without MECP2 mutation were performed.MethodsThe detailed clinical information including clinical manifestation, electroencephalogram (EEG), magnetic resonance imaging (MRI), blood, urine amino acid and organic acid screening of 102 Chinese patients with early-onset epileptic encephalopathies and RTT were collected. CDKL5 gene mutations were analyzed by PCR, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). The patterns of X-chromosome inactivation (XCI) were studied in the female patients with CDKL5 gene mutation.ResultsDe novo CDKL5 gene mutations were found in ten patients including one missense mutation (c.533G > A, p.R178Q) which had been reported, two splicing mutations (ISV6 + 1A > G, ISV13 + 1A > G), three micro-deletions (c.1111delC, c.2360delA, c.234delA), two insertions (c.1791 ins G, c.891_892 ins TT in a pair of twins) and one nonsense mutation (c.1375C > T, p.Q459X). Out of ten patients, 7 of 9 females with Hanefeld variants of RTT and the remaining 2 females with early onset epileptic encephalopathy, were detected while only one male with infantile spasms was detected. The common features of all female patients with CDKL5 gene mutations included refractory seizures starting before 4 months of age, severe psychomotor retardation, Rett-like features such as hand stereotypies, deceleration of head growth after birth and poor prognosis. In contrast, the only one male patient with CDKL5 mutation showed no obvious Rett-like features as females in our cohort. The X-chromosome inactivation patterns of all the female patients were random.ConclusionsMutations in CDKL5 gene are responsible for 7 with Hanefeld variants of RTT and 2 with early-onset epileptic encephalopathy in 71 girls as well as for 1 infantile spasms in 31 males. There are some differences in the phenotypes among genders with CDKL5 gene mutations and CDKL5 gene mutation analysis should be considered in both genders.

Mutational analysis in early-onset familial Alzheimer's disease in Mainland China

Mutations of 3 causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early-onset familial Alzheimer's disease (EOFAD). Recently, a GGGGCC repeat expansion in the noncoding region of C9orf72 was also detected in some patients with clinically diagnosed familial Alzheimer's disease. The prevalence of causative gene mutations in patients with EOFAD has been reported in previous studies but their prevalence remains unclear in Mainland China. The aim of this study was to characterize the common causative gene mutation spectrum and genotype-phenotype correlations in Chinese patients with EOFAD. Genetic screening for mutations in PSEN1, PSEN2, and APP was conducted in a total of 32 families with clinical diagnoses of EOFAD from Mainland China. Subsequently, a hexanucleotide repeat expansion in C9orf72 was detected in all patients. Four novel mutations in PSEN1 (p.A434T, p.I167del, p.F105C, and p.L248P) were identified in 4 respective families, and 1 previously recognized pathogenic mutation in APP (p.V717I) was detected in another 2 unrelated families. The PSEN2 mutation and pathogenic repeat expansions of C9orf72 were not detected in all patients. To the best of our knowledge, this is the first cohort report of a causative gene screen in patients with EOFAD in Mainland China. The analysis of the genetic-clinical correlations in this cohort supports the idea that the clinical phenotype might be influenced by specific genetic defects.

Genotype–phenotype correlation in Chinese patients with pulmonary mixed type adenocarcinoma: Relationship between histologic subtypes, TITF-1/SP-A expressions and EGFR mutations

This study aimed to explore the association between adenocarcinoma-related morphological and molecular characteristics and EGFR mutations in Chinese lung adenocarcinomas. A total of 139 consecutively resected pulmonary adenocarcinoma patients were screened for EGFR mutations by the amplification refractory mutation system assay. For the resected specimens, histologic subtypes were sub-classified using either the 2004 WHO classification or the 2011 IASLC/ATS/ERS classification. Meanwhile, TITF-1 (thyroid transcription factor 1) and SP-A (surfactant-associated protein A) immunohistochemistry staining was also detected. The results were correlated with EGFR mutations and clinicopathological features mentioned above. Both sub-classification methods reflected differences in frequencies of EGFR mutations in lung adenocarcinoma subtypes. In summary, mixed non-mucinous bronchioloalveolar carcinoma (BAC) or papillary components and papillary predominant adenocarcinoma showed a higher frequency of EGFR mutations than mucinous BAC components; Also, EGFR mutations were significantly more common in tumors with TITF-1 or SP-A expressions than in those without (p=0.002, p=0.026), especially the sensitivity of TITF-1 (96.9%) and the negative predictive value of TITF-1 (88.2%). Our data further showed significant genotype–phenotype correlations between EGFR mutations and adenocarcinoma-related morphological and molecular characteristics, and patients with special histologic and IHC staining features might have higher EGFR mutation rates. In addition, this study, for the first time, indicated the significant relationship between SPA IHC and EGFR mutations, which needed confirmation by further research.

Long-Term Benzodiazepine Use in Patients With Major Depressive Disorder in China

There have been no data about long-term benzodiazepine (BZD) use and its correlates in patients with major depressive disorder (MDD) in China. This study aimed to examine the prevalence of long-term BZD use (more than three months) and its demographic and clinical correlates in Chinese patients with MDD. A total of 1,192 patients with MDD were examined in 10 mental health centers in China. Patients' socio-demographic and clinical characteristics and prescriptions for psychotropic drugs were recorded using a standardized form. A large portion of patients (36.2%) received long-term BZD treatment. Univariate analyses revealed that long-term BZD users were older, poorer, and had more impaired occupational functioning than patients not taking BZDs. Long-term BZD users had fewer psychotic symptoms and took less antipsychotic drugs. In multivariate analyses, long-term BZD use was independently associated with older age and more severe impaired occupational functioning; long-term BZD users were less likely to receive antipsychotic medications and traditional antidepressants (tricyclic antidepressants, tetracyclic antidepressant, and monoamine oxidase inhibitors). Long-term BZD use was common in patients with MDD in China. A host of demographic and clinical factors were independently associated with long-term BZD use.

Notch 1 and NF-κB Expression and Clinical Correlation in Chinese Patients with Lymphoblastic Lymphoma

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) is commonly associated with Notch 1 mutations. There is limited data on the relationship between Notch l and NF-κB expression and clinical features in LBL. We evaluated the expression of Notch l and NF-κB in LBL using immunohistochemistry and analyzed their relationship with clinical characteristics, treatment results, and survival. From October 2000 to August 2008, 34 untreated patients with LBL were enrolled in the study. Median age was 11.8 years (range, 1 - 25 years). Twenty-five patients were diagnosed with T-LBL and 9 patients with B-LBL. Most patients received chemotherapy consisting of modified ALL-BFM- 90. Notch l showed high expression in 68% of T-LBL and low expression in 100% of B-LBL (p = 0.015). High expression of Notch l positively correlated with presence of a mediastinal mass but not with 5-year event free survival (EFS) in T-LBL. NF-κB showed high expression in 65% of all patients with LBL, with no difference between T- and B-LBL. NF-κB expression was higher in T-LBL patients with bulky disease and B symptom; it did not correlate with 5-year EFS in T-LBL. Expression of Notch 1 and NF-κB strongly correlated (p = 0.014) in T-LBL. Notch 1 is highly ex- pressed in T-LBL. NF-κB is highly expressed in all patients with LBL with no difference between T-LBL and B-LBL. Notch 1 expression was significantly associated with NF-κB expression in T-LBL. Notch l and NF-κB may play an important role in the development of T-LBL; further investigation is warranted.

Genotype–Phenotype Correlation in Chinese Patients with Dystrophic Epidermolysis Bullosa Pruriginosa

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare variant of dystrophic epidermolysis bullosa (DEB) due to dominant or recessive mutations in the COL7A1 gene. More than 40 mutations in COL7A1 have been described in DEB-Pr. The aim of this study was to understand the genotype-phenotype correlation in Chinese patients with DEB-Pr. Three Chinese families with typical clinical features of DEB-Pr were studied. The results were analysed in association with the eight Chinese DEB-Pr patients reported in the literature. In the three Chinese families with DEB-Pr, we found two dominant cases with G1773R and c.6900+1G>C mutations, and one case with heterozygous G2701W mutation of uncertain inheritance mode. In the 10 Chinese patients with dominant type of DEB-Pr, 7 glycine substitutions and three splicing site mutations of exon 87 skipping were identified. Glycine substitution mutations in the triple helix region and exon 87 skipping, leading to the in-frame deletion of 23 amino acid residues in the triple-helix, are often seen in Chinese patients with dominant DEB-Pr, although the glycine substitutions are also frequently present in dominant DEB.