Genetic Characteristics Of Children Research Articles

Clinical and genetic characteristics of children with acute lymphoblastic leukemia and Li\u2013Fraumeni syndrome

Clinical and genetic characteristics of children with acute lymphoblastic leukemia and Li\u2013Fraumeni syndrome

Clinical, biochemical and genetic characteristics of children with congenital adrenal hyperplasia due to 17α-hydroxylase deficiency.

Objectives Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, that could rarely be due to 17 α-hydroxylase deficiency (17αOHD) and/or 17,20 lyase deficiency. Mutation of CYP17A1 gene causes deficiency of glucocorticoids and androgens but excess of mineralocorticoids. Lack of genital ambiguity in most children causes a delay in diagnosis even until puberty. Classical presentation with hypertension and hypokalemia is often not encountered. We intended to study the clinical, biochemical and genetic characteristics of children diagnosed with CAH due to 17αOHD. Methods Three children who were diagnosed with CAH due to 17αOHD in our institute and on follow up were included in this retrospective study. Clinical, biochemical and genetic characteristics of these children were retrieved and studied from electronic medical records. Results Two children were genetic females and one was genetic male, but all three were raised as females. All had hypertension at diagnosis except one but none had hypokalemia. All of them had mutation in the CYP17A1 gene. The two females responded well to oestrogen and progesterone and had adequate estrogenization clinically. Conclusions Even though CAH due to 17αOHD is quite rare, it should be considered while evaluating young individuals with hypogonadism, hypertension with or without hypokalemia. Lack of genital ambiguity and absence of classical signs at presentation does not rule out this not so uncommon condition and warrants follow up.

Genetic analysis and long-term treatment monitoring of 11 children with glycogen storage disease type IIIa.

Objectives To investigate the clinical and genetic characteristics of children with glycogen storage disease type IIIa (GSD IIIa) and to explore the muscle involvement and manifestations of GSD IIIa patients. Methods The clinical data of 11 patients with GSD IIIa diagnosed by genetic testing from 2003 to 2019 were retrospectively analyzed. Results Twenty variants of AGL gene were detected in 11 patients, eight of which were novel variants. Before treatment, the height was significantly backward. All patients had hepatomegaly. Abnormal biochemical indicators were mainly manifested as significantly increased serum liver and muscle enzymes, accompanied by hypertriglyceridemia, hypoglycemia, hyperlactacidemia, slightly elevated pyruvic acid, and metabolic acidosis. After treatment, the height and liver size of the patients were significantly improved. At the same time, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), lactic acid and pyruvic acid in children were significantly decreased, while creatine kinase (CK) was significantly increased. During follow-up monitoring, six patients developed ventricular hypertrophy. Lactate dehydrogenase (LDH) (691.67±545.27 vs. 362.20±98.66), lactic acid (3.18±3.05 vs. 1.10±0.40), and pyruvic acid (64.30±39.69 vs. 32.06±4.61) were significantly increased in patients with ventricular hypertrophy compared with those without ventricular hypertrophy. Conclusions In clinical cases of upper respiratory tract infection or gastrointestinal symptoms accompanied by hypoglycemia, dyslipidemia, metabolites disorders, elevated serum liver, and muscle enzymes, the possibility of GSD IIIa should be vigilant. During treatment monitoring, if lactic acid, pyruvic acid, LDH, and CK rise, it indicates that the disease is not well controlled and there is the possibility of cardiac hypertrophy.

Clinical and Genetic Spectrum of Children with Primary Ciliary Dyskinesia in China

To report detailed knowledge about the clinical manifestations, ciliary phenotypes, genetic spectrum as well as phenotype/genotype correlation in primary ciliary dyskinesia (PCD) in Chinese children. We recruited 50 Chinese children with PCD. Extensive clinical assessments, nasal nitric oxide, high-speed video analysis, transmission electron microscopy, and genetic testing were performed to characterize the phenotypes and genotypes of these patients. Common clinical features included chronic wet cough (85.4%), laterality defects (70.0%), and neonatal respiratory distress (55.8%). A high prevalence of congenital abnormalities (30.2%, 13/43), observed in patients who underwent comprehensive examination for comorbidities, included thoracic deformity (11.6%, 5/43), congenital heart disease (9.3%, 4/43), and sensorineural deafness (2.3%, 1/43). For 24 children age >6years, the mean predicted values of forced expiratory volume in 1second were 87.2%. Bronchiectasis evident on high-resolution computed tomography was reported in 38.1% of patients (16/42). Biallelic mutations (81 total; 57 novel) were identified in 13 genes: DNAAF3, DNAAF1, DNAH5, DNAH11, CCDC39, CCDC40, CCDC114, CCDC103, HYDIN, CCNO, DNAI1, OFD1, and SPAG1. Overall, ciliary ultrastructural and beat pattern correlated well with the genotype. However, variable phenotypes were also observed in CCDC39 and DNAH5 mutant cilia. This large PCD cohort in China broadens the clinical, ciliary phenotypes, and genetic characteristics of children with PCD. Our findings are roughly consistent with previous studies besides some peculiarities such as high prevalence of associated abnormalities.

Clinical and genetic characteristics of children with STXBP1 encephalopathy

Objective: To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by syntaxin-binding protein 1 (STXBP1) gene mutation. Methods: The clinical data, gene variation and treatment outcome of 15 children with STXBP1 encephalopathy admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2014 to June 2019 were analyzed retrospectively. Results: Among 15 patients, 11 were male and 4 were female, age ranged from 2 months to 69 months. The clinical manifestations of 14 children were epilepsy and developmental delay (DD) and the remaining one showed developmental delay without seizure. The onset age of epilepsy ranged from two days to 19 months and 11 of them experienced the first attack before 1 year of age. The common seizure types were epileptic spasms and tonic seizures. Seven patients were diagnosed with Ohtahara syndrome or West syndrome. Epileptic form discharges were observed in the interictal electroencephalograms (EEG) of 11 patients, including multifocal discharges, suppression-burst and hypsarrhythmia. The brain magnetic resonance imaging of 7 children were abnormal, including myelin dysplasia, less white matter, lack of corpus callosum or hypoplasia. The follow-up time ranged from 2 months to 57 months, after the last follow-up, 3 cases were seizure free, 6 children showed partial response and the other 5 patients had no response on multitherapy. Six of 8 patients showed good responses to levetiracetam (LEV) monotherapy or in combination with other antiepileptic drugs (AEDs). Vigabatrin (VGB) was applied to 5 patients with epileptic spasms and 4 of them showed response. All patients showed different degrees of developmental delay while four of them showed autistic features. STXBP1 gene mutations were identified in all cases and there were 15 types of gene variations, including 8 missense mutations, 1 nonsense mutation, 5 frame shift mutations and 1 complex mutation. Five novel mutations were unreported before, including c.1193A>G, c.172delG, c.1769C>T, c.1038_1039delCC, c.348_351dupTGAA. Conclusions: Development delay and epilepsy are the major and independent clinical phenotypes in children with STXBP1 encephalopathy. The variation of STXBP1 gene is mainly de novo. Levetiracetam and vigabatrin may be more effective in epilepsy control than other AEDs.

Clinical, Laboratory and Genetic Characteristics of Children with GCK-MODY (MODY2): Report of Four Novel Variants in GCK Gene

Objective: Maturity-Onset Diabetes of the Young (MODY) is the most common type of monogenic diabetes. Heterozygous inactivating variants in glucokinase (GCK) gene are related to MODY2 (GCK–MODY). In this study, we aimed to investigate the phenotype and genotype characteristics of patients with GCK–MODY. Methods: Anthropometric and clinical characteristics (age, gender, weight, height and body mass index, complaints, family history), laboratory data (glucose, insulin, glycated hemoglobin, lipid levels) and molecular analysis of the GCK gene were collected from the hospital records. Results: The median age was 9.50 y (1.0–16.0), weight SDS -0.27 (-1.50–2.50), height SDS -0.09 (-2.20–1.60), and body mass index SDS -0.10 (-1.30–2.40). The median level of fasting blood glucose was 121 mg/dL (101–143), insulin was 9.50 mIU/mL (1.80–21.0), and HbA1c was 6.35% (6.20–6.60) at the time of diagnosis. Fourteen patients (78%) were diagnosed incidentally with asymptomatic hyperglycemia, while 4 patients (22%) had symptoms of polyuria and polydipsia. Ten different variants were detected in the GCK gene of 18 cases; one variant was nonsense, one variant was deletion, and the rest of the variants were missense mutations. Exon 7 was the most common location in coding regions and missense was the primary mutation type. The most common variant was c.802G>T (p.Glu268Ter) and detected in 5 (28%) patients. Four (22%) of the variants were novel; seven missense (p.Asp132Gly, p.Arg191Gln, p.Met238Thr, p.Met238Ile, p.Leu243Pro, p.Arg250Cys, p.Arg275Cys), one deletion (p.Pro153del) and one splice site mutation (c.863+3A>G). Conclusion: Since there is no specific treatment for GCK–MODY, GCK gene mutation screening should be considered in cases with early onset mild hyperglycemia, family history of impaired fasting glycemia and negative beta-cell antibodies to avoid unnecessary use of insulin or oral antidiabetic drugs. In this study, ten different variants were detected in the GCK gene of the 18 cases, four of which were novel.

Clinical and genetic characteristics of 62 children with mitochondrial epilepsy

Objective: To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods: Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children's Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ(2) test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results: Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic-clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged-red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex Ⅰ deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m.3243A>G variants, 6 cases had m.8344A>G variants, and 3 cases had m.8993T>G/C variants, m.3271T>C, m.3481G>A, m.3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complex Ⅰ were in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty-three patients were followed up, and the follow-up time was 20 (3-84) months. According to the follow-up results, the anti-epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group (t=1.662, 0.860; P=0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non-first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ(2)=2.794, 0.164, 3.380; P=0.095, 0.686, 0.066). Conclusions: The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic-clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.

Генетическая характеристика детей с целиакией , проживающих на юге России

Генетическая характеристика детей с целиакией , проживающих на юге России

The clinical and genetic characteristics in children with mitochondrial disease in China.

Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing (NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children's Hospital, Capital Medical University from October 2012 to January 2015. In our study, 40 cases of gene confirmed mitochondrial disease including eight kinds of mitochondrial disease, among which Leigh syndrome was identified to be the most common type, followed by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The age-of-onset varies among mitochondrial disease, but early onset was common. All of 40 cases were gene confirmed, among which 25 cases (62.5%) with mitochondrial DNA (mtDNA) mutation, and 15 cases (37.5%) with nuclear DNA (nDNA) mutation. M.3243A>G (n=7) accounts for a large proportion of mtDNA mutation. The nDNA mutations include SURF1 (n=7), PDHA1 (n=2), and NDUFV1, NDUFAF6, SUCLA2, SUCLG1, RRM2B, and C12orf65, respectively.

Clinical and genetic characteristics of children with Leigh syndrome

Objective: To investigate the clinically and genetic characteristics of children with Leigh syndrome. Method: Patients with clinically diagnosed Leigh syndrome(LS)in the department of Neurology, Beijing Children's Hospital from January 2013 to February 2016 underwent the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) detecting with next generation sequencing (NGS) technology. The clinical data of gene confirmed cases were retrospectively collected and analyzed. The differences in the onset age, clinical manifestations, lactic acid level and MRI results between the mtDNA variation and nDNA variation were compared and analyzed.t test, Chi-square test and Fisher's exact test were used for statistical analysis. Result: Thirty-five cases were diagnosed by gene detection, including 20 males and 15 females. The median onset age was 1 year (ranging from the neonatal period to 4.4 years old). The age of onset within 2 years accounted for 74%(26 cases). The onset age of initial symptoms, including developmental delay, developmental regression, and seizures, were 6 (4, 12) months, 12 (8, 14) months, and 6 (1, 23) months respectively. The onset age of ptosis, extrapyramidal symptoms and ataxia were 26 (18, 44) months, 28 (23, 40) months and 28 (19, 35) months, respectively. There were significant differences in the onset age between the three groups (H=21.919, P=0.01). Within the 35 cases, 29 were manifested with developmental delay (83%), 26 with dystonia (74%), 18 with growth retardation, 15 with myasthenia, 13 with developmental regression, 11 with dysphagia, 10 with feeding difficulties, 4 with skeletal dysplasia, and 2 with digestive tract symptoms; nystagmus and respiratory abnormalities were observed in 9 cases respectively; extrapyramidal symptoms, peripheral nerve injury, ptosis, seizures were observed in 8 cases respectively; and ataxia, ophthalmoplegia and hypertrichiasis were found in 5 cases respectively.The blood lactic acid was measured in 32 LS patients, within which 23 cases (72%) had increased results; 8 out of 11 cases who underwent were cerebrospinal fluid lactic acid test had increased results. The results of neuroimaging revealed that all the patients were involved in the brainstem and (or) basal ganglia, of whom 27 (77%) had brainstem involvement, 24 (69%) had basal ganglia involvement. Thirteen out of 14 patients who had medulla oblongata involvement had nDNA variation; while 7 out of 8 patients with cerebellar involvement had nDNA variation. Genetic etiology was confirmed in all patients, among whom there were 17 cases (49%) with mtDNA mutation, including 8993T>C/G (n=5), 14487T>C (n=4), 13513G>A (n=2), 9176T>C, 10158T>C, 3697G>A, 10191T>C, 14459A>G and 11777C>A (n=1) respectively. Remaining 18 cases(51%) had nDNA mutation, including SURF1 gene(n=10), PDHA1 gene(n=3) and one case each of NDUFV1, NDUFAF6, NDUFAF5, NDUFS1 and COQ7 genes. In this study, 27 types of mutations were founded, 15 of which had not been previously reported. Respiratory chain gene mutations have been found in 31 cases(89%); 3 cases had PDHc gene mutations, and 1 case had other mutation. Conclusion: LS usually occurs in infants. The most common primary symptoms are age-dependent abnormal movements, ocular symptoms, and seizures. Respiratory chain defects is the most common causes of LS.SURF1 is the most common variation, followed by 8993T>C/G, 14487 T>C and 13513G>A mutation.

Correction

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 7, No. 3Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published1 Jun 2014https://doi.org/10.1161/HAE.0000000000000005Circulation: Arrhythmia and Electrophysiology. 2014;7:563This article corrects the followingGenetic Characteristics of Children and Adolescents With Long-QT Syndrome Diagnosed by School-Based Electrocardiographic Screening ProgramsIn the article “Genetic Characteristics of Children and Adolescents With Long-QT Syndrome Diagnosed by School-Based Electrocardiographic Screening Programs” by Yoshinaga et al, which was published in the February 2014 issue (Circ Arrhythm Electrophysiol. 2014;7:107–112), corrections were needed.Descriptions about the sites of mutations have been changed in multiple places.The following is the list of mutations changed in Supplemental Table 4. Letters that have been changed are expressed in bold.LQT11) 1252+1 G>A → 1251+1 G>A2) K431X* → K422X*3) T587N → T587MLQT21) The line of “(1760C>T, T587N, Missense, S5/Pore, 0, 1)” has been deleted. This mutation should be one of those in LQT1. We described this mutation in LQT2, too, by mistake.2) 2730 G>C → 2930 G>CLQT31) 5349 G>A → 5350 G>A2) 5963 C>T → 5963 T>GDue to the deletion of one mutation from LQT2, Figure 2 has been revised in order to delete the mutation of “1760C>T” (Figure 2B, inside the purple circle).Last, because one mutation in the clinical group had to be deleted, some words in the text need to be revised.Abstract15 of 16 (94%) → 14 of 15 (93%)Results6 (86%) of 7 → 5 (83%) of 66 (86%) of 7 → 5 (83%) of 6Discussion(6/7; 86%) → (5/6; 83%)The authors apologize for the errors.The online version of the article has been corrected. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesGenetic Characteristics of Children and Adolescents With Long-QT Syndrome Diagnosed by School-Based Electrocardiographic Screening ProgramsMasao Yoshinaga, et al. Circulation: Arrhythmia and Electrophysiology. 2014;7:107-112 June 2014Vol 7, Issue 3 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/HAE.0000000000000005 Originally publishedJune 1, 2014 PDF download Advertisement

Caries preventive efficiency of therapeutic complex accomponying orthodontic treatment of children with initial dental caries.

The use of orthodontic non-removable appliance in orthodontic treatment inter­feres with the process of teeth mineralization, worsens level of oral cavity hygiene, stimulates development of caries process. The situation is complicated when a patient has an initial tooth decay. The aim of this study was to determine genetic characteristics of children with initial caries and clinical evaluation of effectiveness of the developed caries preventive therapeutic complex accompanying treatment of jaw facial anomalies (JFA). 47 children aged 12-14 with initial tooth decay participated in the examination. Complex diagnostics, including molecular genetic studies was carried out. Therapeutic complex for children, of the main group included remineralizing, adaptogenic, biogenic agents, which increase non-specific resistance, as well as infiltration ICON therapy before fixing braces. Caries preventive complex accompanying JFA treatment in children with primary tooth decay developed with regard to revealed genetic disorders of amelogenesis, 2-nd of phase detoxification, collagen formation, functional responses in the oral cavity, state of hard tissues of teeth and periodontal tissues enabled to preserve existing carious process, normalize periodontal and hygienic indices at all stages of treatment.

Genetic Characteristics of Children and Adolescents With Long-QT Syndrome Diagnosed by School-Based Electrocardiographic Screening Programs

A school-based electrocardiographic screening program has been developed in Japan. However, few data are available on the genetic characteristics of pediatric patients with long-QT syndrome who were diagnosed by this program. A total of 117 unrelated probands aged ≤18 years were the subjects who were referred to our centers for genetic testing. Of these, 69 subjects diagnosed by the program formed the screened group. A total of 48 subjects were included in the clinical group and were diagnosed with long-QT syndrome-related symptoms, familial study, or by chance. Mutations were classified as radical, of high probability of pathogenicity, or of uncertain significance. Two subjects in the clinical group died. Genotypes were identified in 50 (72%) and 23 (48%) of subjects in the screened and clinical groups, respectively. Of the KCNQ1 or KCNH2 mutations, 31 of 33 (94%) in the screened group and 15 of 16 (94%) in the clinical group were radical and of high probability of pathogenicity. Prevalence of symptoms before (9/69 versus 31/48; P<0.0001) and after (12/69 versus 17/48; P=0.03) diagnosis was significantly lower in the screened group when compared with that in the clinical group although the QTc values, family history of long-QT syndrome, sudden death, and follow-up periods were not different between the groups. These data suggest that the screening program may be effective for early diagnosis of long-QT syndrome that may allow intervention before symptoms. In addition, screened patients should have follow-up equivalent to clinically identified patients.

Genetic characteristics of children and adolescents with long QT syndrome diagnosed by school-based electrocardiographic screening programs

Genetic characteristics of children and adolescents with long QT syndrome diagnosed by school-based electrocardiographic screening programs

Sporadic unilateral retinoblastoma or first sign of bilateral disease?

BackgroundA small number of children with unilateral retinoblastoma later develop retinoblastoma in the contralateral eye (metachronous bilateral retinoblastoma).MethodsWe analysed the clinical and genetic characteristics of children with sporadic unilateral retinoblastoma...