[Effects of acute paraquat poisoning on cognitive ability in humans].

Objective: To explore the effects of acute paraquat poisoning on cognitive function of patients through neuropsychologic test. Methods: In June 2019, 36 patients with acute paraquat poisoning in the emergency department of a provincial hospital in Hebei Province were selected as the case group. 36 healthy individuals were selected as control group. The cognitive function and depressive state were assessed by mini mental state scale, auditory word learning test, digit span test, connection test, Boston Naming Test and geriatric depression scale. Results: The results of Mini-Mental State examination showed that the total score of the case group was lower than that of the control group, the difference was statistically significant (P<0.05) . The results of the Auditory Vocabulary Learning test showed that the scores of delayed recall, clue recall, corrective ability and semantic learning strategies of the case group were significantly lower than those in the control group (P<0.05) . There was no significant difference in the scores of immediate memory between the two groups (P>0.05) . The scores of Digit Span test and Boston Naming test in the control group were higher than those in the case group, the Trail Making test time in the control group was shorter than that in the case group, and the differences were statistically significant (P<0.05) . Conclusion: Acute paraquat poisoning can impair human cognitive ability to a certain extent.

Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development.

Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development. Importantly, two autism-associated truncations, R205X and E239X, were shown to be Dyrk1a loss-of-function mutants. Studies of the truncated Dyrk1a mutants may provide new insights into the role of Dyrk1a in brain development, as well as the role of Dyrk1a loss of function in the pathophysiology of autism.

[Clinical investigation of ultrasound-guided percutaneous nephrolithotomy accessed by SVOF-principle and two-step puncture techniques].

Objective: To evaluate the safety and effectiveness of ultrasound-guided percutaneous nephrolithotomy (PCNL) accessed by SVOF-principle and two-step puncture techniques. Methods: A total of 838 cases with upper urinary stones underwent percutaneous nephrolithotomy successfully accessed by ultrasound-guided between June 2007 and December 2015 at Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Of all cases were divided in two groups: hydronephrosis calyces puncture group include 425 cases and SVOF-principle puncture group include 413 cases. The access establishment time, operation time, stone free rate (SFR), postoperative complications, and postoperative hospitalization time between the two groups we compared by t test or χ2 test. Results: Statistically significant differences were observed between hydronephrosis calyces puncture group and SVOF-principle puncturegroup in the first access establishment time ((16.5±8.4) minutes vs. (11.2±5.9) minutes, t=3.931, P=0.013), one-stage SFR (74.3% vs. 85.7%, χ2=16.868, P=0.000), postoperative hospitalization time ((6.4±2.1) days vs. (4.8±1.8)days, t=4.574, P=0.000), transfusion rate (7.1% vs. 2.9%, χ2=8.027, P=0.006), and embolization rate (3.3% vs. 1.0%, χ2=5.390, P=0.020). There were no statistically significant differences in operation time, total SFR, postoperative fever and sever infection between these two groups (all P>0.05). In both two groups, no serious complications such as peripheral organ injury and death occurred. Conclusions: PCNL accessed guided by ultrasound with SVOF-principle and two-step puncture techniques has advantages of quick puncture location, high stone free rate, fewer complications and fast recovery. This technique is an effective and safe treatment option for upper urinary stones and deserved promotion and application in clinic.

Association analysis between HFM1 variation and primary ovarian insufficiency in Chinese women.

HFM1 is a meiosis-specific gene and expressed in germ-line tissues. More recently, evidence has indicated that variations in HFM1 gene could be causative for primary ovarian insufficiency (POI), also known as premature ovarian failure. The aim of this study was to investigate the association between HFM1 gene variants and sporadic POI in Chinese women. A total of 138 POI patients and 316 healthy controls (matched for ethnic background, sex, and age of the patients) were recruited in this study. We screened the entire HFM1 coding region by direct sequencing in all subjects and identified six variants of HFM1 gene in POI group, namely c.148G>A/p.Glu50Lys, c.1241A>C/p.His414Pro, c.2325C>A/p.Phe775Leu, c.3367T>C/p.Ser1123Pro, c.3580C>T/p.Arg1194Cys, and c.1686-1G>C. The variation rate of HFM1 in POI group is significantly higher than control group (p < 0.01). The p.His414Pro and p.Arg1194Cys were predicted to be probably damaging to the HFM1 protein function, while p.Glu50Lys, p.Phe775Leu and p.Ser1123Pro mutants might not have any deleterious effect on the structure or function of the protein by online predictors. Taken together, our data suggested that HFM1 gene might be associated with primary ovarian insufficiency in Chinese population.

[The relationship between myocardial bridge in mural coronary artery segment and coronary atherosclerosis].

Objective: The myocardial bridging (MB) prevalence, anatomic characteristics of MB, and the relationship between characteristics of MB in mural coronary artery segment and coronary atherosclerosis were analyzed. Methods: In this perspective nonrandomized controlled study, a total of 1 132 patients who admitted to our hospital for suspected or known coronary artery disease from January 2012 to June 2013 were enrolled. All patients underwent dual-source 64-slice spiral CT coronary angiography. The general patient characteristics including gender, age, history of hypertension, diabetes, hyperlipidemia and smoking, serum level of total cholesterol (TC) and LDL-C were recorded. The length, depth and the degree of compression of myocardial bridge in systolic or diastolic phase were also analyzed in patients with MB. The relationship between MB and coronary atherosclerosis, the characteristics of MB and coronary atherosclerosis were analyzed by Spearman correlation analysis, univariate logistic regression analysis, variate logistic regression analysis and linear regression analysis. Results: Myocardial bridging was detected in 330 out of 1 132 patients, and MB was mostly located in the mural coronary artery (329/330) and at the mid-distal segment of the left anterior descending artery (LAD). Average MB length was 20.1 mm (3.3-95.5 mm) and the average depth was 2.13 mm (0.24-12.40 mm). There were 140 patients with intramyocardial MB (42.6%) and 189 patients with superficial MB (57.4%). Myocardial bridging was an independent protective factor of coronary atherosclerosis (OR=0.361, P=0.000) and the proximal segment of MB was more susceptible to atherosclerosis compared to the distal segment of MB (P=0.000). Multivariate analysis revealed that age, hypertension and the degree of compression of myocardial bridge in diastolic phase were independent factors related to the atherosclerosis (odds ratio: 1.064, 2.186 and 1.049 respectively, P value: 0.000, 0.002 and 0.000). The depth of MB was significantly correlated with systolic or diastolic narrowing(OR: 4.227, 3.398 and P value: 0.000, 0.001). Conclusions: The prevalence of myocardial bridging is 29% in this patient cohort. The proximal segment of myocardial bridging in mural coronary artery is more susceptible to atherosclerosis. In addition, the depth of myocardial bridging and the degree of compression of myocardial bridge in diastolic phase are the independent factors related to atherosclerosis.

The effect of TRPM7 suppression on the proliferation, migration and osteogenic differentiation of human dental pulp stem cells.

AIM: To investigate the role of the Ca(2+) -Mg(2+) ion channel TRPM7 in the proliferation, migration and osteogenic differentiation of human dental pulp stem cells (hDPSCs). METHODOLOGY: Immunohistochemistry was used to localize expression of TRPM7 in human dental pulp tissues and in cultured hDPSCs. Isolated hDPSCs were infected with recombinant lentiviruses expressing short hairpin RNA (shRNA) specific for TRPM7, or control shRNA, in order to suppress TRPM7 mRNA expression and investigate its functional role. The proliferation of the shRNA-infected hDPSCs was evaluated using both an MTT assay to measure viable cell numbers and cell cycle analysis. Cell migration was assessed using a transwell assay. The dynamic mRNA expression of TRPM7 during osteogenic differentiation of hDPSCs and the effect of shRNA specific for TRPM7 on hDPSC osteogenic differentiation were evaluated by real-time PCR. RESULTS: TRPM7 expression was widespread in human dental pulp tissue and was detected mainly in the cytomembrane and cytoplasm of hDPSCs. Suppression of TRPM7 inhibited both the proliferation and the migratory capacity of hDPSCs. TRPM7 mRNA expression was elevated during osteogenic differentiation of hDPSCs. TRPM7-specific shRNA inhibited osteogenic differentiation of hDPSCs, with downregulated mRNA expression of the osteogenic markers alkaline phosphatase (ALP), dentine sialophosphoprotein (DSPP), bone sialoprotein (BSP), runt-related transcription factor (RUNX2) and osterix (OSX). CONCLUSIONS: TRPM7 was involved in the regulation of hDPSC proliferation, migration and osteogenic differentiation and may play a role in the dental pulp repair process.

Prenatal diagnosis of chromosomal abnormalities in fetuses with abnormal cardiac ultrasound findings: evaluation of chromosomal microarray-based analysis.

OBJECTIVES: To assess the frequency of karyotype abnormalities and chromosome 22q11.2 deletion syndrome among fetuses with abnormal cardiac ultrasound findings, and to evaluate the clinical value of chromosomal microarray-based analysis (CMA) in the study of such pregnancies. METHODS: First, we carried out retrospective analysis of karyotype abnormalities and 22q11.2 deletion syndrome cases diagnosed between January 2009 and December 2011 in our center among fetuses with abnormal cardiac ultrasound findings (n = 276). Second, CMA was performed in 51 of the fetuses with such findings, normal karyotype and negative or no 22q11.2 deletion syndrome study, and in the only fetus with a heart defect and an apparently balanced de novo chromosomal rearrangement. RESULTS: Out of the 276 pregnancies with abnormal cardiac ultrasound findings, karyotyping revealed a chromosomal abnormality in 44 (15.9%). Of fetuses with normal karyotype in which 22q11.2 deletion syndrome studies were performed, 6.4% (5/78) had this microdeletion syndrome. Among fetuses with abnormal cardiac findings, normal karyotype and negative or no 22q11.2 deletion syndrome study that underwent CMA, the detection rate of pathogenic copy number variants not detected by conventional cytogenetics was 2.0% (1/51), and no variants of uncertain clinical significance were found. In the fetus with a heart defect and an apparently balanced de novo chromosomal rearrangement, CMA revealed that the rearrangement was not truly balanced. CONCLUSIONS: In the assessment of genetic abnormalities in pregnancies with abnormal cardiac ultrasound findings, the diagnostic yield may be increased by 2% if CMA is used as a complementary tool to conventional cytogenetics. Our results suggest that CMA could be a good alternative to karyotyping in these pregnancies.

A recurrent 1.71 Mb genomic imbalance at 2q13 increases the risk of developmental delay and dysmorphism.

Whole genome profiling such as array comparative genomic hybridization has identified novel genomic imbalances. Many of these genomic imbalances have since been shown to associate with developmental delay, intellectual disability and congenital malformation. Here we identified five unrelated individuals who have a recurrent 1.71 Mb deletion/duplication at 2q13 (Human Genome Build 19: 111,392,197-113,102,594). Four of these individuals have developmental issues, four have cranial dysmorphism. Literature review revealed 14 more cases that had similar genomic imbalances at 2q13. Many of them had developmental delay and dysmorphism. Taken together, 93% and 63% of individuals with this genomic imbalance displayed impaired developmental skills and/or abnormal facial features respectively. This copy number variant (CNV) has not been reported in normal control databases. We, therefore, propose that CNV in this region is a risk factor for developmental delay and dysmorphism.

[Effect of hypochloric acid on Escherichia coli biofilm and the clinical efficacy of hypochloric acid for wounds with Escherichia coli infection].

Objective: To investigate the effect of hypochloric acid on Escherichia coli biofilm and the clinical efficacy of hypochloric acid for wounds with Escherichia coli infection. Methods: One strain of Escherichia coli with the strongest bacterial biofilm forming ability among the strains isolated from specimens in 25 patients (16 males and 9 females, aged 32-67 years) from five clinical departments of the 940th Hospital of the Joint Logistic Support Force was collected for the experimental study from September to December 2019. The Escherichia coli was cultured with hypochloric acid at 162.96, 81.48, 40.74, 20.37, 10.18, 5.09, 2.55, 1.27, 0.64, and 0.32 µg/mL respectively to screen the minimum bactericidal concentration (MBC) of hypochloric acid. The Escherichia coli was cultured with hypochloric acid at the screened MBC for 2, 5, 10, 20, 30, and 60 min respectively to screen the shortest bactericidal time of hypochloric acid. The biofilm formation of Escherichia coli was observed by scanning electron microscopy at 6, 12, 24, 48, 72, and 96 h of incubation, respectively. After 72 h of culture, hypochloric acid at 1, 2, 4, 8, and 16 times of MBC was respectively added to Escherichia coli to screen the minimum biofilm eradicate concentration (MBEC) of hypochloric acid against Escherichia coli. After hypochloric acid at 1, 2, 4, and 8 times of MBEC and sterile saline were respectively added to Escherichia coli for 10 min, the live/dead bacterial staining kit was used to detect the number of live and dead cells, with the rate of dead bacteria calculated (the number of samples was 5). From January to December 2020, 41 patients with infectious wounds meeting the inclusion criteria and admitted to the Department of Burns and Plastic Surgery of the 940th Hospital of Joint Logistic Support Force of PLA were included into the prospective randomized controlled trial. The patients were divided into hypochloric acid group with 21 patients (13 males and 8 females, aged (46±14) years) and povidone iodine group with 20 patients (14 males and 6 females, aged (45±19) years) according to the random number table. Patients in the 2 groups were respectively dressed with sterile gauze soaked with hypochloric acid of 100 µg/mL and povidone iodine solution of 50 mg/mL with the dressings changed daily. Before the first dressing change and on the 10th day of dressing change, tissue was taken from the wound and margin of the wound for culturing bacteria by agar culture method and quantifying the number of bacteria. The amount of wound exudate and granulation tissue growth were observed visually and scored before the first dressing change and on the 3rd, 7th, and 10th days of dressing change. Data were statistically analyzed with one-way analysis of variance, Dunnett-t test, independent sample t test, Mann-Whitney U test, Wilcoxon signed-rank test, chi-square test, or Fisher's exact probability test. Results: The MBC of hypochloric acid against Escherichia coli was 10.18 µg/mL, and the shortest bactericidal time of hypochloric acid with MBC against Escherichia coli was 2 min. Escherichia coli was in a completely free state after 6 and 12 h of culture and gradually aggregated and adhered with the extension of culture time, forming a mature biofilm at 72 h of culture. The MBEC of hypochloric acid against Escherichia coli was 20.36 µg/mL. The Escherichia coli mortality rates after incubation with hypochloric acid at 1, 2, 4, and 8 times of MBEC for 10 min were significantly higher than that after incubation with sterile saline (with t values of 6.11, 25.04, 28.90, and 40.74, respectively, P<0.01). The amount of bacteria in the wound tissue of patients in hypochloric acid group on the 10th day of dressing change was 2.61 (2.20, 3.30)×104 colony forming unit (CFU)/g, significantly less than 4.77 (2.18, 12.48)×104 CFU/g in povidone iodine group (Z=2.06, P<0.05). The amounts of bacteria in the wound tissue of patients in hypochloric acid group and povidone iodine group on the 10th day of dressing change were significantly less than 2.97 (2.90, 3.04)×106 and 2.97 (1.90, 7.95)×106 CFU/g before the first dressing change (with Z values of 4.02 and 3.92, respectively, P<0.01). The score of wound exudate amount of patients in hypochloric acid group on the 10th day of dressing change was significantly lower than that in povidone iodine group (Z=2.07, P<0.05). Compared with those before the first dressing change, the scores of wound exudate amount of patients in hypochloric acid group on the 7th and 10th days of dressing change were significantly decreased (with Z values of -3.99 and -4.12, respectively, P<0.01), and the scores of wound exudate amount of patients in povidone iodine group on the 7th and 10th days of dressing change were significantly decreased (with Z values of -3.54 and -3.93, respectively, P<0.01). The score of wound granulation tissue growth of patients in hypochloric acid group on the 10th day of dressing change was significantly higher than that in povidone iodine group (Z=2.02, P<0.05). Compared with those before the first dressing change, the scores of wound granulation tissue growth of patients in hypochloric acid group on the 7th and 10th days of dressing change were significantly increased (with Z values of -3.13 and -3.67, respectively, P<0.01), and the scores of wound granulation tissue growth of patients in povidone iodine group on the 7th and 10th days of dressing change were significantly increased (with Z values of -3.12 and -3.50, respectively, P<0.01). Conclusions: Hypochloric acid can kill Escherichia coli both in free and biofilm status. Hypochloric acid at a low concentration shows a rapid bactericidal effect on mature Escherichia coli biofilm, and the higher the concentration of hypochloric acid, the better the bactericidal effect. The hypochloric acid of 100 µg/mL is effective in reducing the bacterial load on wounds with Escherichia coli infection in patients, as evidenced by a reduction in wound exudate and indirect promotion of granulation tissue growth, which is more effective than povidone iodine, the traditional topical antimicrobial agent.

ERCC6 founder mutation identified in Finnish patients with COFS syndrome.

Cerebro-oculo-facio-skeletal (COFS) syndrome is an autosomal recessive disorder characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. We report a large consanguineous pedigree from northern Finland with six individuals belonging into four different sibships and affected with typical COFS syndrome phenotype. Two deceased patients have been published previously in 1982 as the first cases exhibiting cerebral calcifications typical for this disorder. Two living and one of the deceased patients were all shown to possess a novel homozygous mutation in the ERCC6 [Cockayne syndrome B (CSB)] gene, thereby confirming the diagnosis on molecular genetic level even for the earlier published cases. Genealogical investigation showed a common ancestor living in a northeastern village in Finland in the 18th century for all six patients implying a founder effect.

Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders.

BACKGROUND: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. PATIENTS: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. RESULTS: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers approximately 1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover approximately 500 kb (chr15:28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. CONCLUSIONS: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.

Dual heterogeneous structures lead to ultrahigh strength and uniform ductility in a Co-Cr-Ni medium-entropy alloy.

Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 µm) and ultra-fine grains (0.5∼2 µm), together with heterogeneous L12-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L12 nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.

Genetic analysis of first-trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH.

Miscarriage is the spontaneous loss of an embryo or fetus before the 20th week of pregnancy. Most miscarriages occur before the end of the first trimester (<13 weeks). Although many risk factors relate to this occurrence, genetic factors play the most important role. Chromosomal abnormalities, including both numerical and structural anomalies, underlie the majority of miscarriages. In this study, we employed a comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)-based genotyping, and microarray-based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first-trimester miscarriages of Chinese women. Seventy cases (61%) were found to have chromosomal anomalies, of which 90% were numerical and 10% were structural. Cytogenetic karyotyping identified 78.6% (55/70), PCR assays 2.9% (2 triploids), and arrayCGH 18.6% (13/70) of the anomalies. In this study, a microdeletion of 108 kb and four microduplications sizing from 300 to 1460 kb were observed. An advantage of using this combination approach is that microsatellite genotyping and arrayCGH can be accomplished in spite of culture failure and maternal cell contamination. In addition, arrayCGH can detect submicroscopic chromosomal anomalies and gene dosage alterations.

[Advances in the research of antibacterial properties and composite materials of nanometer zinc oxide].

Nanometer zinc oxide has become a new hotspot in the research of tissue engineering materials due to its excellent antibacterial properties, biocompatibility, and anti-tumor properties. In this paper, the existing research results were summarized, generalized, and analyzed. The antibacterial mechanism of nanometer zinc oxide was discussed in depth. The antibacterial properties and advantages of the latest nanometer zinc oxide composite materials were introduced in detail. In this review, we made prospect of the future application of nanometer zinc oxide.

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

Reduced Penetrance of PRRT2 Mutation in a Chinese Family With Infantile Convulsion and Choreoathetosis Syndrome.

Paroxysmal kinesigenic dyskinesia is a rare episodic movement disorder that can be isolated or associated with benign infantile seizures as part of choreoathetosis syndrome. Mutations in the PRRT2 gene have been recently identified as a cause of paroxysmal kinesigenic dyskinesia and infantile convulsion and choreoathetosis (ICCA). We reported a PRRT2 heterozygous mutation (c.604-607delTCAC, p.S202Hfs*25) in a 3-generation Chinese family with infantile convulsion and choreoathetosis and paroxysmal kinesigenic dyskinesia. The mutation was present in 5 family members, of which 4 were clinically affected and 1 was an obligate carrier with reduced penetrance of PRRT2. The affected carriers of this mutation presented with a similar type of infantile convulsion during early childhood and developed additional paroxysmal kinesigenic dyskinesia symptoms later in life. In addition, they all had a dramatic clinical response to oxcarbazepine/phenytoin therapy. Reduced penetrance of the PRRT2 mutation in this family could warrant genetic counseling.

Deletion of the entire NF1 gene causing distinct manifestations in a family.

We identified a father and son with neurofibromatosis type 1 (NF1) due to a deletion of the entire NF1 gene detected by fluorescence in situ hybridization (FISH). As is the case for others reported to have such large deletions, father and son had severe NF1, including a large number of cutaneous neurofibromas, facial anomalies, large hands, feet, and head, and developmental impairment. They were discordant in that seizures and plexiform neurofibromas occurred only in the propositus. Large NF1 deletions can be compatible with familial transmission and appear to be associated with a distinct phenotype.

CHARGE association in a child with de novo inverted duplication (14)(q22-->q24.3).

We report on a 4-1/2 year old girl with apparent CHARGE association who had a de novo inverted duplication (14)(q22-->24.3), iris colobomas, ventricular septal defect, soft tissue choanal atresia, intellectual impairment, growth retardation, sensorineural deafness, apparently low set ears, and upslanting palpebral fissures. Family history was unremarkable and parental chromosomes were normal. Similarities between this and previously reported cases of 14q duplication suggest that a locus for a gene or genes causing some of the anomalies of CHARGE association may reside in the region 14q22 to 24.3.

Deletion of the entire NF1 gene detected by the FISH: four deletion patients associated with severe manifestations.

Genetic analysis of NF1 has indicated a wide diversity of mutations, including chromosome rearrangements, deletions, insertions, duplications, and point mutations. Recently, five severely affected individuals have been found by Kayes et Al. [1994] to have deletions encompassing the entire gene. These deletions were detected by quantitative Southern analysis. To simplify deletion detection, we have employed fluorescence in situ hybridization (FISH) using intragenic probes. Thirteen unrelated individuals with NF1 have been studied. Among six with severe manifestations, four have been found to have deletions detected by probes cFF13, cFB5D, cP5, yA43A9, yA113D7 and yD8F4. All four deletions patients have severe developmental delay, minor and major anomalies (including one with bilateral iris colobomas), and multiple cutaneous neurofibromas or plexiform neurofibromas which were present before age 5 years. FISH provides a simple and rapid means of identification of NF1 gene deletions and will allow more rigorous testing of the hypothesis that such deletions are associated with severe manifestations.

Distal 8p deletion (8)(p23.1): an easily missed chromosomal abnormality that may be associated with congenital heart defect and mental retardation.

We describe the clinical manifestations and molecular cytogenetic analyses of three patients with a similar distal deletion of chromosome 8. Each child had mild developmental delay and subtle minor anomalies. Two had cardiac anomalies but no other major congenital anomalies were present. High resolution G and R banding showed in all three patients del(8)(p23.1), but the breakpoint in case 1 was distal to 8p23.1, in case 2 was in the middle of 8p23.1, and in case 3 proximal to 8p23.1. Fluorescence in situ hybridization (FISH) studies with a chromosome 8 paint probe confirmed that no other rearrangement had occurred. FISH with a chromosome 8-specific telomere probe indicated that two patients had terminal deletions. Chromosome analysis of the parents of case 1 and mother of case 2 were normal; the remaining parents were not available for study. Thirteen individual patients including the three in this study, and three relatives in one family with del(8)(p23.1), have been reported in the past 5 years. Major congenital anomalies, especially congenital heart defects, are most often associated with a breakpoint proximal to 8p23.1. Three patients were found within a 3-year period in this study and five cases were found within 4 years by another group, indicating that distal 8p deletion might be a relatively common chromosomal abnormality. This small deletion is easily overlooked (i.e., cases 1 and 2 were reported as normal at amniocentesis) and can be associated with few or no major congenital anomalies.