scholarly journals Analysis of clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia that is spontaneously relieved

Endocrine ◽  
2021 ◽  
Author(s):  
Zi-di Xu ◽  
Pei-pei Hui ◽  
Wei Zhang ◽  
Qiao Zeng ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Birth Weight ◽  
Mutation Analysis ◽  
Age Of Onset ◽  
Gene Mutations ◽  
Spontaneous Remission ◽  
Effective Rate ◽  
Chinese Children ◽  
Genetic Characteristics ◽  
Number Of Children ◽  
Pathogenic Genes

Abstract Objective This study aimed to analyze the clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia (CHI) that is spontaneously relieved. Methods The patient group comprised 200 children with CHI that were treated at the Beijing Children’s Hospital from January 2006 to December 2018. The patients were divided into two groups according to their prognosis: the spontaneous remission group (n = 92) and the nonspontaneous remission group (n = 108). The clinical characteristics, pathogenic genes, diagnosis and treatment process, and follow-up data of both groups were analyzed retrospectively. Results Of the 200 children with CHI, 92 achieved spontaneous remission. The age of spontaneous remission was between one month and nine years, and 47 of the children were relieved before the age of one year. The median age of onset was 85 days (range: 1–2825 days) in the spontaneous remission group and 2 days (range: 1–210 days) in the nonspontaneous remission group (P < 0.05). The mean birth weight was 3.44 ± 0.76 kg for the spontaneous remission group and 3.95 ± 0.75 kg for the nonspontaneous remission group (P < 0.05). Of the 92 children in the spontaneous remission group, 65 were treated with diazoxide with effective rate of 81.5% (53/65). In 12 cases in which diazoxide treatment failed, octreotide was used with an effective rate of 83.3% (10/12). Of the 108 children in the nonspontaneous remission group, 88 were treated with diazoxide with an effective rate of 43.2 % (38/88), and 29 children were treated with octreotide with an effective rate of 48.28% (14/29). Of the 30 children in the spontaneous remission group that underwent mutation analysis of CHI-related pathogenic genes, 10 children (10/30, 33.3%) carried mutations. Of the 48 children in the nonspontaneous remission group that underwent mutation analysis of CHI-related pathogenic genes, 37 children (37/48, 77.1%) were found to carry mutations. All of the differences in the indices mentioned above were statistically significant. Conclusions The rate of spontaneous remission of CHI was significantly higher in children with late age of CHI onset, light birth weight, effective diazoxide treatment, and no common pathogenic gene mutations. Spontaneous remission was also possible for a small number of children that carried mutations in the ABCC and KCNJ11 genes and in whom diazoxide treatment failed.

scholarly journals Analysis on the pathogenic genes of 60 Chinese children with congenital hyperinsulinemia

2018 ◽  
Vol 7 (12) ◽  
pp. 1251-1261
Author(s):  
Zi-Di Xu ◽  
Wei Zhang ◽  
Min Liu ◽  
Huan-Min Wang ◽  
Pei-Pei Hui ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Gene Mutations ◽  
Chinese Children ◽  
Treatment Modalities ◽  
Partial Pancreatectomy ◽  
Genetic Characteristics ◽  
Pathogenic Genes ◽  
Second Generation Sequencing ◽  
Long Term Prognosis

This study aims to summarize and analyze the clinical manifestations, genetic characteristics, treatment modalities and long-term prognosis of congenital hyperinsulinemia (CHI) in Chinese children. Sixty children with CHI, who were treated at Beijing Children’s Hospital from January 2014 to August 2017, and their families, were selected as subjects. The CHI-related causative genes in children were sequenced and analyzed using second-generation sequencing technology. Furthermore, the genetic pathogenesis and clinical characteristics of Chinese children with CHI were explored. Among the 60 CHI children, 27 children (27/60, 45%) carried known CHI-related gene mutations: 16 children (26.7%) carried ABCC8 gene mutations, seven children (11.7%) carried GLUD1 gene mutations, one child carried GCK gene mutations, two children carried HNF4α gene mutations and one child carried HADH gene mutations. In these 60 patients, eight patients underwent 18F-L-DOPA PET scan for the pancreas, and five children were found to be focal type. The treatment of diazoxide was ineffective in these five patients, and hypoglycemia could be controlled after receiving partial pancreatectomy. In conclusion, ABCC8 gene mutation is the most common cause of CHI in Chinese children. The early genetic analysis of children’s families has an important guiding significance for treatment planning and prognosis assessment.

scholarly journals Two novel mutations in the ALPL gene of unrelated Chinese children with Hypophosphatasia: case reports and literature review

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G > C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G > C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions In this study, six mutations in the ALPL gene were found in four Chinese HPP patients, two of which were novel: c.359G > C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G > C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G>C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results show that the novel mutation c.359G>C is strongly indicated to be disease-causing and associated with severe infantile form of HPP.

scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G>C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Risk of Low Birth Weight According to Household Composition in Brussels and Montreal: Do Income Support Policies Variations Explain the Differences Observed between Both Regions?

2021 ◽  
Vol 18 (15) ◽  
pp. 7936
Author(s):  
Mouctar Sow ◽  
Myriam De Spiegelaere ◽  
Marie-France Raynault
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Household Composition ◽  
Income Support ◽  
Welfare Benefits ◽  
Number Of Children ◽  
Households With Children ◽  
Vulnerable Households ◽  
Welfare Families ◽  
The Impact

Variations in social policy between countries provide opportunities to assess the impact of these policies on health inequities. This study compares the risk of low birth weight in Brussels and Montreal, according to household composition, and discusses the impact of income support policies. For each context, we estimated the impact of income support policies on the extent of poverty of welfare recipients, using the model family method. Based on the differences found, we tested hypotheses on the association between low birth weight and household composition, using administrative data from the birth register and social security in each region. The extent of poverty of welfare families differs according to household composition. In Quebec, the combination of low welfare benefits and larger family allowances widens the gap between households with children and those without children. The risk of LBW also differs between these two contexts according to the number of children. Compared to children born into large welfare families, first-born children are more at risk in Montreal than in Brussels. In addition to the usual comparative studies on the topic, our study highlights the importance of an evaluative perspective that considers the combination of different types of income support measures to better identify the most vulnerable households.

4-Jahres-Update der Murano-Studie bestätigt den Stellenwert von Venetoclax in der 2. Therapielinie der CLL

2021 ◽  
pp. 77-79
Author(s):  
Maximilian Schmutz ◽  
Sebastian Sommer
Keyword(s):  
Response Rate ◽  
Residual Disease ◽  
Gene Mutations ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Fixed Duration ◽  
Genetic Characteristics ◽  
Genomic Complexity ◽  
End Of Treatment

<b>Purpose:</b> In previous analyses of the MURANO study, fixed-duration venetoclax plus rituximab (VenR) resulted in improved progression-free survival (PFS) compared with bendamustine plus rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics. <b>Patients and methods:</b> Patients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR. PFS, overall survival (OS), peripheral-blood minimal residual disease (MRD) status, genomic complexity (GC), and gene mutations were assessed. <b>Results:</b> Of 389 patients, 194 were assigned to VenR and 195 to BR. Four-year PFS and OS rates were higher with VenR than BR, at 57.3% and 4.6% (hazard ratio [HR], 0.19; 95% CI, 0.14 to 0.25), and 85.3% and 66.8% (HR, 0.41; 95% CI, 0.26 to 0.65), respectively. Undetectable MRD (uMRD) at end of combination therapy (EOCT) was associated with superior PFS compared with low MRD positivity (HR, 0.50) and high MRD positivity (HR, 0.15). Patients in the VenR arm who received ibrutinib as their first therapy after progression (n = 12) had a reported response rate of 100% (10 of 10 evaluable patients); patients subsequently treated with a venetoclax-based regimen (n = 14) had a reported response rate of 55% (six of 11 evaluable patients). With VenR, the uMRD rate at end of treatment (EOT) was lower in patients with GC than in those without GC (<i>P</i> = 0.042); higher GC was associated with shorter PFS. Higher MRD positivity rates were seen with <i>BIRC3</i> and <i>BRAF</i> mutations at EOCT and with <i>TP53, NOTCH1, XPO1,</i> and <i>BRAF</i> mutations at EOT. <b>Conclusion:</b> Efficacy benefits with fixed-duration VenR are sustained and particularly durable in patients who achieve uMRD. Salvage therapy with ibrutinib after VenR achieved high response rates. Genetic mutations and GC affected MRD rates and PFS. <b>Trial registration:</b> ClinicalTrials.gov NCT02005471.

scholarly journals Preliminary Study on the Clinical and Genetic Characteristics of Hereditary Spherocytosis in 15 Chinese Children

2021 ◽  
Vol 12 ◽  
Author(s):  
Chongjun Wu ◽  
Ting Xiong ◽  
Zhongjin Xu ◽  
Chunlei Zhan ◽  
Feng Chen ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Clinical Characteristics ◽  
Hemoglobin Concentration ◽  
Chinese Children ◽  
Test Results ◽  
Test Analysis ◽  
Genetic Characteristics ◽  
Significant Difference ◽  
Gene Test

ObjectiveTo investigate the clinical and genetic characteristics of hereditary spherocythemia (HS) in Chinese children, and to analyze the potential genotypic/phenotypic associations.MethodsThe clinical data and gene test results of children with HS were collected. All patients were diagnosed by gene test results, and the laboratory results were obtained before splenectomy. The data of red blood cell (RBC), hemoglobin (HB), mean red blood cell volume (MCV), mean red blood cell hemoglobin (MCH), mean red blood cell hemoglobin concentration (MCHC), and hematocrit (HCT) were statistically analyzed according to different mutation genes. Statistical methods for comparison between groups Mann–Whitney test analysis, two-terminal p &lt; 0.05 was considered significant difference.ResultsA total of 15 children were enrolled in our hospital, and 14 variants were found (nine variants have not been reported before), including 10 ANK1 mutations (seven ANK1 truncated mutations) and five SPTB mutations. Patients with ANK1 mutations had more severe anemia than those with SPTB mutations (significantly lower RBC, HB, MCHC, and HCT).ConclusionThis is one of the few studies on the genetic and clinical characteristics of children with HS in China. This study identified the unique genetic and clinical characteristics of Chinese children with HS and analyzed the pathogenic genotype–phenotypic association. The results confirmed that the anemia degree of HS patients caused by ANK1 was more serious than that of patients with SPTB deficiency. However, further study of the correlation between genotype and phenotype requires a larger sample size.

scholarly journals Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunli Wei ◽  
Ting Xiao ◽  
Jingliang Cheng ◽  
Jiewen Fu ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
The Novel ◽  
Pathogenic Variants ◽  
Pathogenic Genes ◽  
Compound Heterozygous Variants ◽  
Normal Controls

Abstract As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.

scholarly journals The Clinical Spectrum of Young Onset Dementia Points to Its Stochastic Origins

2021 ◽  
pp. 1-17
Author(s):  
Peter K. Panegyres
Keyword(s):  
Small Vessel Disease ◽  
Age Of Onset ◽  
Gene Mutations ◽  
Lewy Body Disease ◽  
Corticobasal Degeneration ◽  
Young Onset ◽  
Clinical Presentations ◽  
Eeg Data ◽  
Common Causes ◽  
Young Onset Dementia

Background: Dementia is a major global health problem and the search for improved therapies is ongoing. The study of young onset dementia (YOD)—with onset prior to 65 years—represents a challenge owing to the variety of clinical presentations, pathology, and gene mutations. The advantage of the investigation of YOD is the lack of comorbidities that complicate the clinical picture in older adults. Here we explore the origins of YOD. Objective: To define the clinical diversity of YOD in terms of its demography, range of presentations, neurological examination findings, comorbidities, medical history, cognitive findings, imaging abnormalities both structural and functional, electroencephagraphic (EEG) data, neuropathology, and genetics. Methods: A prospective 20-year study of 240 community-based patients referred to specialty neurology clinics established to elucidate the nature of YOD. Results: Alzheimer’s disease (AD; n = 139) and behavioral variant frontotemporal (bvFTD; n = 58) were the most common causes with a mean age of onset of 56.5 years for AD (±1 SD 5.45) and 57.1 years for bvFTD (±1 SD 5.66). Neuropathology showed a variety of diagnoses from multiple sclerosis, Lewy body disease, FTD-MND, TDP-43 proteinopathy, adult-onset leukoencephalopathy with axonal steroids and pigmented glia, corticobasal degeneration, unexplained small vessel disease, and autoimmune T-cell encephalitis. Non-amnestic forms of AD and alternative forms of FTD were discovered. Mutations were only found in 11 subjects (11/240 = 4.6%). APOE genotyping was not divergent between the two populations. Conclusion: There are multiple kinds of YOD, and most are sporadic. These observations point to their stochastic origins.

Sign in / Sign up

Export Citation Format

Share Document