Genetic and phenotypic analysis of 225 Chinese children with developmental delay and/or intellectual disability using whole-exome sequencing.

Developmental delay (DD), or intellectual disability (ID) is a very large group of early onset disorders that affects 1-2% of children worldwide, which have diverse genetic causes that should be identified. Genetic studies can elucidate the pathogenesis underlying DD/ID. In this study, whole-exome sequencing (WES) was performed on 225 Chinese DD/ID children (208 cases were sequenced as proband-parent trio) who were classified into seven phenotype subgroups. The phenotype and genomic data of patients with DD/ID were further retrospectively analyzed. There were 96/225 (42.67%; 95% confidence interval [CI] 36.15-49.18%) patients were found to have causative single nucleotide variants (SNVs) and small insertions/deletions (Indels) associated with DD/ID based on WES data. The diagnostic yields among the seven subgroups ranged from 31.25 to 71.43%. Three specific clinical features, hearing loss, visual loss, and facial dysmorphism, can significantly increase the diagnostic yield of WES in patients with DD/ID (P = 0.005, P = 0.005, and P = 0.039, respectively). Of note, hearing loss (odds ratio [OR] = 1.86%; 95% CI = 1.00-3.46, P = 0.046) or abnormal brainstem auditory evoked potential (BAEP) (OR = 1.91, 95% CI = 1.02-3.50, P = 0.042) was independently associated with causative genetic variants in DD/ID children. Our findings enrich the variation spectrums of SNVs/Indels associated with DD/ID, highlight the value genetic testing for DD/ID children, stress the importance of BAEP screen in DD/ID children, and help to facilitate early diagnose, clinical management and reproductive decisions, improve therapeutic response to medical treatment.

Seizure course of PCDH19 clustering epilepsy in female children: A multicentre cohort study in China.

AIM: To investigate the seizure course of PCDH19 clustering epilepsy (PCDH19-CE) in a cohort of female children in China. METHOD: This ambidirectional cohort study examined 113 female patients with PCDH19-CE through multicentre collaboration. Prognostic factors for seizure freedom were evaluated by multivariate Cox regression analysis. RESULTS: The median seizure course period from seizure onset was 6 years 6 months. Of 113 patients, 78% and 56% experienced seizure freedom for at least 1 year and at least 2 years respectively. In patients younger than 5 years (n = 30), 5 to 10 years (n = 52), and older than 10 years (n = 31), 57%, 81%, and 94% experienced at least 1 year of seizure freedom, and 32%, 52%, and 84% experienced at least 2 years of seizure freedom, respectively. However, 58% (65 out of 113) relapsed at least once after more than 1 year of seizure freedom without trigger exposure (40%) or because of common triggers, including fever (43%) and antiseizure medication (ASM) reduction (29%). There was an 84% risk of seizure relapse after ASM reduction attempts. The likelihood of seizure freedom decreased with early age at seizure onset and developmental delay. INTERPRETATION: Patients with PCDH19-CE exhibit increasing seizure freedom with age, but there is a risk of relapse. ASM reduction in children younger than 10 years old requires caution. Patients with early seizure onset and developmental delay have a reduced chance of seizure freedom.

Competitive adsorption characteristics of VOCs and water vapor by activated carbon prepared from Fe/N-doped pistachio shell.

Various materials have been developed to capture volatile organic compounds (VOCs) to mitigate air pollution. However, sorbent materials with excellent resistance to water are rare. Here, several Fe/N-doped activated carbons (ACs) have been prepared to capture VOCs in humid environments. The ACs were analyzed by various characterization techniques, such as BET, SEM, XPS, XRD, FTIR, and Raman. The results showed that Fe/N doping resulted in the specific surface area of the ACs increasing by 500 to 1000 m2 g-1, the average pore size increasing to approximately 2 nm, improved mesoporous structure, higher graphitization, lower hydrophilicity, and polarity. The VOCs adsorption performance of the ACs was evaluated by static and dynamic adsorption experiments. The uptake of toluene and ethyl acetate by ACs was enhanced to 224 mg g-1 and 135 mg g-1, respectively. And ACs were able to maintain 70 to 80% VOCs adsorption capacity for VOCs at 80% relative humidity. Furthermore, the microscopic mechanisms were investigated by the grand canonical Monte Carlo method (GCMC). The highly graphitized structure and the N functional groups favored the VOC adsorption process and discouraged the adsorption of water vapor. This work affirmed the dominance of Fe/N-doped carbon, which will contribute to the evolution of water-resistant VOCs adsorbent materials.

The effects of early combined training on the physical development of preterm infants with different gestational ages.

Objective: To investigate the effects of early combined training on the physical development of preterm infants of different gestational ages. Methods: A total of 144 preterm infants from our hospital's neonatal intensive care unit (NICU) between 2019 and 2020 were selected as the research participants and randomly divided into an intervention group (77 cases) and a control group (67 cases). The physical development and catch-up growth satisfaction rate of preterm infants in the intervention and control groups were compared at 40 weeks, 3 months, 6 months and 12 months of corrected age. Results: At 40 weeks of gestational age and corrected 3 months of gestational age, the physical growth indexes of the intervention group were higher than those of the control group, with a statistical difference (P < 0.05). At the corrected age of 12 months, the body weight and length of preterm infants in the <29 weeks intervention group were still higher than those in the control group (P < 0.05). The body weight of preterm infants in the 29-32 weeks and 32-34 weeks intervention groups was higher than in the control group (P < 0.05). There was no statistical difference between the intervention and control groups in the 34-37 weeks category (P > 0.05). The catch-up growth satisfaction rates of all the physical growth indexes in the intervention group were higher than those of the control group at the corrected 3 months for all the gestational ages (P < 0.05). While those indexes in the three >29 weeks intervention groups were higher than those in the <29 weeks intervention group at the corrected age of 12 months (P < 0.05). Conclusion: Early combined training can promote the early catch-up growth of preterm infants, especially in the early gestational age groups (<34 weeks), and the catch-up growth promotion can last for 12 months. The older the gestational age, the sooner catch-up growth satisfaction will occur.

Effect of nitrogen functional groups on competitive adsorption between toluene and water vapor onto nitrogen-doped spherical resorcinol-formaldehyde resin-based activated carbon.

To elucidate the effect of nitrogen functional groups on the competitive adsorption of toluene and water vapor, a series of N-doped resorcinol-formaldehyde resin-based activated carbons using g-C3N4 as the nitrogen source were prepared, which possessed different N contents (1.29-6.14%). The competitive adsorption characteristics and mechanisms were investigated by characterizations, dynamic adsorption experiments, adsorption isotherms, and density functional theory calculations. Results showed that the normalized toluene adsorption capacity under 50 RH% was consistent with the N content, revealing that nitrogen functional groups can enhance the competitive adsorption for toluene under a humid atmosphere. Adsorption isotherms analysis suggested that nitrogen functional groups can not only accelerate the adsorption of toluene but also improve the hydrophobicity of carbon surface. Competitive adsorption mechanisms were ascribed to π-π interactions and electrostatic interactions. Specifically, graphitic-N and pyridinic-N enhance competitive adsorption for toluene through reinforced π-π interactions with toluene and weakened electrostatic interactions with water molecule. However, pyrrolic-N improve the competitive adsorption, which is principally attributed to enhanced π-π interactions with toluene. Furthermore, it was found that the reusability of activated carbon could be improved by nitrogen functional groups. This study provides theoretical hints to develop volatile organic compound adsorbents in the presence of water vapor.

Case Report: Identification of Two Variants of ALG13 in Families With or Without Seizure and Binocular Strabismus: Phenotypic Spectrum Analysis.

Background: Genetic causes in most affected children with intellectual disability and/or development delay remain unknown. Methods: To identify potential variants responsible for these disorders, we recruited 161 affected families and performed whole-exome sequencing and associated bioinformatics analysis. Results: In the present study, we report the identification of variants in the ALG13 gene in two of the families. In family 1, a known pathogenic missense variant (c.23T > C; p.V8A) of ALG13 was identified in a boy and his mother. In family 2, a novel missense variant (c.862C > G; p.L288V) of the same gene was identified in the affected boy and his phenotypically normal mother. Genotype-phenotype correlation analysis by comparing reported 28 different variants (HGMD) showed that three major phenotypes, including various seizures/epilepsy, intellectual disability, and development delay (such as growth, speech, motor, etc.), are present in most affected individuals. However, other phenotypes, such as strabismus and absence of seizure in our second patient, are not reported if any, which may represent a unique case of X-linked recessive nonsyndromic disorder caused by a mutation in ALG13. Conclusion: We identified two missense variants in ALG13 in a cohort of 161 families with affected individuals diagnosed as intellectual disability and/or development delay. A novel c.862C > G mutation may represent a case of X-linked recessive.

A Novel Variant of the CHD2 Gene Associated With Developmental Delay and Myoclonic Epilepsy.

Pathogenic variants in CHD2 have been reported to have a wide range of phenotypic variability in neurodevelopmental disorders, such as early-onset epileptic encephalopathy, developmental delay, and behavior problems. So far, there is no clear correlation between genotypes and phenotypes. This study reports a Chinese patient with a novel heterozygous CHD2 mutation (c.4318C>T, pArg1440*). Her main clinical manifestations include developmental delay, myoclonic epilepsy, and hypothyroidism. Then, we reviewed a total of 144 individuals carrying CHD2 variants with epileptic encephalopathy. In terms of clinical manifestations, these patients are usually described with variable epilepsy phenotypes, including idiopathic photosensitive occipital epilepsy, Dravet syndrome, Jeavons syndrome, Lennox-Gastaut syndrome, juvenile myoclonic epilepsy, and non-specific epileptic encephalopathy. Among them, myoclonic seizures and generalized tonic-clonic seizures are the main seizure types in all patients hosting CHD2 single-nucleotide or indel variants (non-CNVs). At the molecular level, there are 102 types of CHD2 non-CNVs in 126 patients, almost one mutational type corresponding to one person, and there is no difference in the incidence ratio of each position. Furthermore, we summarized that a small proportion of patients inherited CHD2 variants, and not all patients with CHD2 variants had seizures. Importantly, the phenotypes, especially seizures control and fever sensitivity, and genotypes had a relative association. These results enriched the database of CHD2-relative neurodevelopmental disorders and provided a theoretical foundation for researching the relationship between genotypes and phenotypes.

Alkylation modified pistachio shell-based biochar to promote the adsorption of VOCs in high humidity environment.

The objective of this work was to evaluate the adsorption capacity of alkylated modified porous biochar prepared by esterification and etherification (PSAC-2) for low concentrate volatile organic compounds (VOCs, toluene and ethyl acetate) in high humidity environment by experiments and theoretical calculations. Results showed that PSAC-2 has a large specific surface area and weak surface polarity, at 80% relative humidity, its capacities for toluene and ethyl acetate adsorption could be maintained at 92% and 87% of the initial capacities (169.9 mg/g and 96.77 mg/g). The adsorption behaviors of toluene, ethyl acetate, and water vapor were studied by adsorption isotherms, and isosteric heat was obtained. The desorption activation energy was obtained by temperature programmed desorption experiment. The outcomes manifested that the PSAC-2 can achieve strong adsorption performance for weakly polar molecules. Through density functional theory (DFT) simulations, owing to the interaction of hydrogen bonds, oxygen-containing groups became a significant factor influencing the adsorption of VOCs in humid environments. These results could provide an important reference for VOCs control in a high humidity environment.

Adsorption/desorption characteristics of low-concentration semi-volatile organic compounds in vapor phase on activated carbon.

The adsorption/desorption behaviors of semi-volatile organic compounds (SVOCs: 1,2,3,4-tetrachlorobenzene (TCB) and phenol) in vapor phase by activated carbon (AC) were investigated by the experiments and density functional theory calculation. Investigations showed that at 100-160 °C, the adsorption capacities of TCB and phenol on AC were in the range of 176.6-342.0 mg/g and 24.0-66.4 mg/g, respectively. Increasing the temperature inhibited the SVOCs adsorption. TCB tended to be adsorbed on AC surface by monolayer, whereas the phenol was multilayer adsorption. The stronger interaction between SVOCs and active sites resulted in a higher desorption temperature (TCB: 255-689 °C; phenol: 200-369 °C). The SVOCs adsorption on AC was fitted well by the pseudo-first-order kinetic model, their lower concentration and larger molecular structure influenced the AC external mass transfer and intraparticle diffusion. TCB and phenol were adsorbed on graphite layer by a parallel manner, their highest adsorption energies were -75.59 kJ/mol and -55.00 kJ/mol, respectively. Oxygen-containing groups altered the charge distribution of the atoms at the edge of the graphite layer, which improved the SVOCs adsorption through enhancement of electrostatic interactions and formation of hydrogen bonds. The carboxyl and lactone groups played a critical role in improving the TCB adsorption capacity, while the carboxyl was important for phenol adsorption.

Generation of an iPSC line (SMCPGi001-A) from a patient with Bain type X-linked mental retardation syndrome carrying HNRNPH2 gene mutation.

Bain type X-linked mental retardation syndrome is an X-linked dominant neurodevelopmental disorder characterized by psychomotor developmental delay and intellectual disability. The rare syndrome is caused by HNRNPH2 gene mutation. In this study, the iPSC cell line (SMCPGi001-A) was acquired by Sendai virus-mediated iPSC reprogramming from the peripheral blood mononuclear cells (PBMCs) obtained from a 1-year-old girl with de novo p.R206W mutation in the HNRNPH2 gene. The identification experiments of stemness and differentiation potential of three germ layers showed that the cell line had pluripotent stem cell characteristics and the potential of tridermal differentiation.

The adsorption properties of microporous activated carbon prepared from pistachio nut shell for low-concentration VOCs under low-medium temperatures.

The control of low-concentration VOCs in coal-fired flue gas is one of the research hotspots at present. In this work, K2CO3 and K2CO3-KCl were employed to activate the agricultural wastes (pistachio nut shell) to prepare activated carbon (AC), named PSAC-1 and PSAC-2, respectively. By testing the adsorption performance of the prepared AC and commercial activated carbon (CAC) for the five target VOCs, it was observed that the adsorption capacity of PSAC-2 was the best compared to the other two. Particularly, the adsorption capacity of PSAC-2 (225 mg·g-1) for phenol was 3.8 times that of CAC (59 mg·g-1). In addition, the pseudo-first-order model, pseudo-second-order model, and Elovich model all fitted the adsorption process well, which indicated that both physical adsorption and chemical adsorption existed simultaneously, in which physical adsorption played a dominant role and chemical adsorption played a minor role. Weber-Morris kinetic model was used to illustrate the rate-controlling mechanism; the results confirmed that the stage of external membrane mass transfer was the control stage of adsorption rate. The results of this study can provide some references for the commercial production of biomass-derived AC and the removal of VOCs in coal-fired flue gas.

Removal characteristics of organic pollutants by the adsorbent injection coupled with bag filtering system.

Activated carbon (AC) injection coupled with bag filtering (ACI+BF) is a promising technology for the organic pollutant treatment in the flue gas of coal-fired power plants. The removal characteristics of six volatile organic compounds (VOCs) and adsorption pathways were investigated in a self-designed ACI+BF system. The results suggested that o-xylene had the highest removal efficiency and that was the lowest for benzene, which was influenced by their boiling points and saturated vapor pressures. The physicochemical properties of AC changed slightly after VOCs adsorption in the ACI+BF system. The VOCs removal process was dominated by physical adsorption even if the adsorption temperature was higher. With the increasing of adsorption temperature and VOCs concentration, the removal efficiency reduced; while that increased with increasing the AC feeding rate and residence time. The VOCs removal by the ACI+BF system could be divided into two processes, including the adsorption in pipeline and adsorption in the bag filter. Bag filter had an important contribution to the total removal efficiency. Increasing the length of the pipeline and reducing the dust cleaning frequency of the filter bag were useful in enhancing the organic pollutants removal efficiency.

Three intellectual disability-associated de novo mutations in MECP2 identified by trio-WES analysis.

BACKGROUND: To date, at least 746 genes have been identified to cause intellectual disability (ID). Among them, mutations in the Methyl CpG binding protein 2 (MECP2) gene are the leading cause of Rett syndrome and associated ID. METHODS: Considering the large number of ID-associated genes, we applied trio-based whole-exome sequencing (trio-WES) and in silico analysis for genetic diagnosis of 294 children with ID. RESULTS: Three de novo heterozygous mutations [NM_004992.3: c.502C > T, p.(Arg168*), c.916C > T, p.(Arg306Cys), and c.879C > G, p.(Ile293Met)] in MECP2 were identified in three unrelated girls. The first two mutations were detected in two patients who were diagnosed as typical Rett syndrome, X-linked ID and psychomotor retardation. The third mutation (c.879C > G), a previously unreported, was found in a 6-year-old girl with ID, microcephaly, severe underweight and psychomotor retardation. Particularly, this extremely rare de novo mutation (DNM) is located in the transcriptional repression domain (TRD) of MECP2, where at least 62 different causal mutations are identified. CONCLUSIONS: We identified three DNMs in MECP2 in a cohort of 294 individuals with ID. The novel c.879C > G mutation, as a likely pathogenic allele, may become a risk factor associated with X-linked ID, microcephaly and psychomotor retardation.

Gene-Focused Networks Underlying Phenotypic Convergence in a Systematically Phenotyped Cohort With Heterogeneous Intellectual Disability.

The broad spectrum of intellectual disability (ID) patients' clinical manifestations, the heterogeneity of ID genetic variation, and the diversity of the phenotypic variation represent major challenges for ID diagnosis. By exploiting a manually curated systematic phenotyping cohort of 3803 patients harboring ID, we identified 704 pathogenic genes, 3848 pathogenic sites, and 2075 standard phenotypes for underlying molecular perturbations and their phenotypic impact. We found the positive correlation between the number of phenotypes and that of patients that revealed their extreme heterogeneities, and the relative contribution of multiple determinants to the heterogeneity of ID phenotypes. Nevertheless, despite the extreme heterogeneity in phenotypes, the ID genes had a specific bias of mutation types, and the top 44 genes that ranked by the number of patients accounted for 39.9% of total patients. More interesting, enriched co-occurrent phenotypes and co-occurrent phenotype networks for each gene had the potential for prioritizing ID genes, further exhibited the convergences of ID phenotypes. Then we established a predictor called IDpred using machine learning methods for ID pathogenic genes prediction. Using10-fold cross-validation, our evaluation shows remarkable AUC values for IDpred (auc = 0.978), demonstrating the robustness and reliability of our tool. Besides, we built the most comprehensive database of ID phenotyped cohort to date: IDminer http://218.4.234.74:3100/IDminer/, which included the curated ID data and integrated IDpred tool for both clinical and experimental researchers. The IDminer serves as an important resource and user-friendly interface to help researchers investigate ID data, and provide important implications for the diagnosis and pathogenesis of developmental disorders of cognition.

De novo SCN1A, SCN8A, and CLCN2 mutations in childhood absence epilepsy.

This study aimed to identify monogenic mutations from Chinese patients with childhood absence epilepsy (CAE) and summarize their characteristics. A total of 100 patients with CAE were recruited in Peking University First Hospital from 2005 to 2016 and underwent telephone and outpatient follow-up review. We used targeted disease-specific gene capture sequencing (involving 300 genes) to identify pathogenic variations for these patients. We identified three de novo epilepsy-related gene mutations, including missense mutations of SCN1A (c. 5399 T > A; p. Val1800Asp), SCN8A (c. 2371 G > T; p. Val791Phe), and CLCN2 (c. 481 G > A; p. Gly161Ser), from three patients, separately. All recruited patients presented typical CAE features and good prognosis. To date, CAE has been considered a complex disease caused by multiple susceptibility genes. In this study, we observed that 3% of typical CAE patients had a de novo mutation of a known monogenic epilepsy-related gene. Our study suggests that a significant proportion of typical CAE cases may be monogenic forms of epilepsy. For genetic generalized epilepsies, such as CAE, further studies are needed to clarify the contributions of de novo or inherited rare monogenic coding, noncoding and copy number variants.

Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing.

Background The mutations of thiamine pyrophosphokinase-1 (TPK1) gene have been frequently studied in some patients with thiamine metabolism dysfunction syndrome-5 (THMD5), while TPK1 mutations in Chinese patients have been investigated by only homozygous. A search of the literature on the mutations in the Chinese population currently published revealed that no reports of compound heterozygous mutations were reported. Here, we report a Chinese patient with compound heterozygous TPK1 mutations who underwent magnetic resonance imaging (MRI), whole exome sequencing (WES), molecular diagnosis, bioinformatics analysis, and three-dimensional (3D) protein structure analysis. Case presentation A Chinese boy was born after an uneventful pregnancy to non-consanguineous and healthy parents. On the sixth day after his birth, the lactate level of the patient was between 8.6 mmol/L and 14.59 mmol/L in plasma (the normal level is in the range of 0.5-2.2 mmol/L). Lactate was reduced to the normal level after rehydration, acid correction, expansion, and other treatments. After 4 months, the patient presented with an acute, 3-h-long, non-induced convulsions, and was admitted to our hospital for weakness, decreased oral intake, and lethargy. Results achieved by electroencephalography (EEG), cerebrospinal fluid, and other biochemical findings were normal. A visible hemorrhagic lesion was also observed in the brain. Seizures increased significantly during infection, which was accompanied by higher lactic acid levels. MRI of the brain showed an obvious signal shadow, in which bilateral frontal and temporal parietal subarachnoid cavities were widened, and more abnormal signals were observed; therefore, further consideration of hypoxic-ischemic encephalopathy and genetic metabolic disease was taken into account. Conclusions The results of WES revealed that the patient was associated with compound heterozygous mutations NM_022445.3:c.[263G>A]; [226A>G] of TPK1. His parents were non-consanguineous; while his father was found to be a heterozygous carrier with the mutation c.[263G>A], his mother was identified as a heterozygous carrier with the mutation c.[226A>G]. The results indicated that the patient had a compound heterozygous TPK1 mutation, and this is the first reported case in China.

Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria.

BACKGROUND: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons. CASE PRESENTATION: We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic. CONCLUSION: We predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations.

[Detection of subtelomeric copy number variations in children with intellectual disability].

OBJECTIVE: To detect subtelomeric copy number variations in children with genetic intellectual disability (ID) using multiplex ligation-dependent probe amplification (MLPA), and to investigate the pathogenesis of genetic ID. METHODS: A total of 68 children with ID who had normal results of G-banding karyotype analysis were included in the study. Their subtelomeric copy number variations were detected using MLPA P036. RESULTS: Among the 68 children with ID, 7(10%) showed subtelomeric copy number variations, and all the variations were deletion mutations. Among them, 1 case carried 2 subtelomeric microdeletions, and 1 case carried 4 subtelomeric microdeletions. CONCLUSIONS: Subtelomeric copy number variations are important causes of genetic ID. MLPA can be used as an economic and effective method for investigating the pathogenesis of genetic ID.

[Analysis of MLC1 gene mutation in a Chinese family with megalencephalic leukoencephalopathy with subcortical cysts].

The clinical data of a patient with megalencephalic leukoencephalopathy (MLC) with subcortical cysts and her parents were collected. MLC1 gene mutation was detected by polymerase chain reaction and direct DNA sequencing. The patient presented with motor developmental delay and giant skull, and brain magnetic resonance imaging showed diffuse white matter swelling accompanied by subcortical cysts in bilateral frontal and parietal lobes. Gene sequencing identified two heterozygous mutations of MLC1, including missense mutation in exon 3 (c.217G>A, p.Gly73Arg) and splice site mutation in intron 9 (c.772-1G>C in IVS9-1). The patient's parents both had heterozygous mutation c.772-1G>C in IVS9-1 with normal phenotype. It can be presumed that c.772-1G>C in IVS9-1 comes from the parents, and c.217G>A (p.Gly73Arg) is a de novo mutation.

Perinatal occipital lobe injury in children: analysis of twenty-one cases.

This study used magnetic resonance imaging to analyze causes and clinical courses of pediatric occipital lobe injury. Patients undergoing magnetic resonance imaging for suspected bilateral occipital lobe injury at our Neurodevelopmental Department between July 2007 and June 2011 were included. We evaluated magnetic resonance imaging characteristics, clinical courses, electroencephalogram monitoring, and Denver Development Screen Test scores. Twenty-one infants were examined. Of these, 10 had been born preterm. Thirteen patients demonstrated hypoglycemia. Perinatal period hypoglycemia comprised the most common cause (71.4%) of occipital brain injury. Visual abnormalities were evident in 18 patients. Seventeen (80.9%) patients manifested epilepsy. Infantile spasms were observed in 13 cases (76.5%). According to Denver Development Screen Test assessment, 17 patients demonstrated delayed motor development. Motor function and language improved in 10 patients after effective control of their seizures. Hypoglycemia constitutes the most common cause of occipital injury in infants. Visual impairment, startle episodes, infantile spasms, and motor developmental delay comprise the most common complications, whereas language function is usually spared.