scholarly journals Clinical, Neuroimaging, Biochemical, and Genetic Features in Cases of Chinese Patients with Adrenomyeloneuropathy

2019 ◽  
Author(s):  
Jie Li ◽  
Hongfen Wang ◽  
Zizi He ◽  
Xiangqing Wang ◽  
Jing Tang ◽  
...  
Keyword(s):  
Plasma Levels ◽  
De Novo ◽  
Brain Mri ◽  
Positive Family History ◽  
Spastic Paraparesis ◽  
The Other ◽  
Chinese Patients ◽  
De Novo Mutation ◽  
Abcd1 Gene ◽  
Long Chain

Abstract Background: Adrenoleukodystrophy is a rare neurogenetic disease,adrenomyeloneuropathy is the most common adult phenotype, such patients in China have not gotten enough attention.This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods: We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results: All 6 patients are men. Ages of neurological symptom onset distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison's disease. Four patients were diagnosed as pure AMN, the other two patients with cerebral involvement. Four patients have abnormalities of nerve conduction studies. There are four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion: This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Mental stimulation may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene. Keywords: Adrenomyeloneuropathy, Addison disease, Spastic paraparesis, Very long chain fatty acid, ABCD1.

scholarly journals Clinical, Neuroimaging, Biochemical, and Genetic Features in Six Chinese Patients with Adrenomyeloneuropathy

2019 ◽  
Author(s):  
Jie Li ◽  
Hongfen Wang ◽  
Zizi He ◽  
Xiangqing Wang ◽  
Jing Tang ◽  
...  
Keyword(s):  
Plasma Levels ◽  
De Novo ◽  
Brain Mri ◽  
Positive Family History ◽  
Clinical Analysis ◽  
The Other ◽  
Chinese Patients ◽  
De Novo Mutation ◽  
Abcd1 Gene ◽  
Genetic Features

Abstract Background Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention.This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results All 6 patients are men. Ages of neurological symptom onset are distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison's disease. Four patients were diagnosed as pure AMN, while the other two patients were with cerebral involvement. Four patients had abnormalities of nerve conduction studies. There were four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients were found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Emotional trauma may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene.

scholarly journals Clinical, neuroimaging, biochemical, and genetic features in six Chinese patients with Adrenomyeloneuropathy

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jie Li ◽  
Hongfen Wang ◽  
Zizi He ◽  
Xiangqing Wang ◽  
Jing Tang ◽  
...  
Keyword(s):  
Plasma Levels ◽  
De Novo ◽  
Brain Mri ◽  
Positive Family History ◽  
Clinical Analysis ◽  
The Other ◽  
Chinese Patients ◽  
De Novo Mutation ◽  
Abcd1 Gene ◽  
Genetic Features

Abstract Background Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention. This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results All 6 patients are men. Ages of neurological symptom onset are distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison’s disease. Four patients were diagnosed as pure AMN, while the other two patients were with cerebral involvement. Four patients had abnormalities of nerve conduction studies. There were four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients were found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Emotional trauma may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene.

scholarly journals De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Zhixin Jiang ◽  
Yinan Zhang ◽  
Jingbin Yan ◽  
Fengwen Li ◽  
Xinqian Geng ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Clinical Features ◽  
Mitochondrial Function ◽  
Peripheral Blood ◽  
De Novo ◽  
Brain Mri ◽  
De Novo Mutation ◽  
Function Evaluation ◽  
Ros Generation ◽  
Spontaneous Mutant

Background. The syndrome of maternally inherited diabetes and deafness (MIDD) is typically caused by the m.3243A>G mutation and widely considered maternally inherited. In our study, we aimed to investigate the heredity way of the m.3243A>G among pedigrees with MIDD and discover novel mitochondrial DNA mutations related to atypical clinical phenotypes.Methods. Heteroplasmy levels of the m.3243A>G mutation in peripheral blood, saliva, and urine sediment of 31 individuals from 10 unrelated pedigrees were measured by pyrosequencing. Clinical evaluations including endocrinological, audiological, and magnetic resonance imaging (MRI) examinations, mitochondrial function evaluation in peripheral blood mononuclear cells (PBMCs), and whole mitochondrial DNA (mtDNA) sequencing were performed among the spontaneous mutant pedigrees.Results. Among the 10 unrelated MIDD pedigrees, we found that the de novo m.3243A>G mutation occurred in the family 1957 (F1957). The proband (F1957-II-1) and her son (F1957-III-1) both manifested diabetes with mild bilateral sensorineural hearing loss (SNHL) and abnormal brain MRI, and F1957-III-1 also complained of severe nausea and vomiting. Mitochondrial function evaluation in PBMCs revealed an increased level of ROS generation and decreased levels of ATP and mitochondrial membrane potential (ΔΨm) in the two m.3243A>G carriers. Whole mtDNA sequencing also revealed a de novo heteroplasmic substitution at m.16093T>C in both the proband and her son.Conclusions. Our study showed that de novo m.3243A>G mutation accompanied by other point mutations may occur in the very early embryonic or germ cell stage without maternal inheritance, bringing about both typical and atypical clinical features.

Untargeted lipidomics of ovine milk to analyse the influence of different diet regimens

2021 ◽  
pp. 1-4
Author(s):  
Cristina Manis ◽  
Margherita Addis ◽  
Maria Sitzia ◽  
Paola Scano ◽  
Viviana Garau ◽  
...  
Keyword(s):  
Mammary Gland ◽  
De Novo ◽  
Partial Least Square ◽  
Least Square ◽  
The Other ◽  
Sheep Grazing ◽  
Multivariate Statistical ◽  
Lipid Mobilization ◽  
Saturated Medium ◽  
Long Chain

Abstract In this work we report a lipidomics approach to study the effects of two diet systems on the composition of ovine milk. Milk from two groups of Sarda sheep grazing on 40% (P40) and 60% (P60) of pasture were analyzed by a UHPLC-QTOF-MS analytical platform and data submitted to multivariate statistical analysis. Pairwise partial least square discriminant analysis of the lipid profile of the data was carried out to classify samples and to find discriminant lipids. The two dietary groups were characterized by differences in triacylglycerols, phosphocholines and phosphatidylethanolamines levels. Discriminants of the P40 group were TG and PC containing in their backbone saturated medium chain FA thus suggesting greater de novo fatty synthesis in the mammary gland. On the other hand, the P60 group was characterized by TG and PC formed by unsaturated long chain FA originating from the diet or from lipid mobilization.

A novel case of congenital spinocerebellar ataxia 5: further support for a specific phenotype associated with the p.(Arg480Trp) variant in SPTBN2

2020 ◽  
Vol 13 (12) ◽  
pp. e238108
Author(s):  
Andrea Zonta ◽  
Alessandro Brussino ◽  
Patrizia Dentelli ◽  
Alfredo Brusco
Keyword(s):  
De Novo ◽  
Brain Mri ◽  
Spastic Paraparesis ◽  
Lower Limbs ◽  
Normal Brain ◽  
Hereditary Ataxia ◽  
Missense Change ◽  
History Of ◽  
Brain Ventricle ◽  
Vermian Hypoplasia

A 4-year-old girl was referred to the geneticist with a history of ataxia associated with intention tremor of the hands, strabismus and hypermetropy. Her symptoms presented about 2 years earlier with inability to walk unaided and lower limbs hypotonia. Cognitive functions were normal. Brain MRI showed a cerebellar and vermian hypoplasia with enlargement of both the cerebrospinal fluid spaces and the IV brain ventricle. Family history was unremarkable. A genetic screening using a 42-gene panel for hereditary ataxia/spastic paraparesis identified a de novo c.1438C>T - p.(Arg480Trp) missense change in the SPTBN2 gene (NM_006946.2). This variant is reported to be associated with congenital ataxia, later evolving into ataxia and intellectual disability. This case further supports the existence of a specific SPTBN2 p.(Arg480Trp)-associated phenotype, with a de novo recurrence of this variant in the heterozygous state.

P902Danon disease: clinical features and outcomes

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Brambatti ◽  
Y Esshaki ◽  
S Vanam ◽  
V Escobedo ◽  
G Macias ◽  
...  
Keyword(s):  
Clinical Features ◽  
Clinical Presentation ◽  
De Novo ◽  
Positive Family History ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Rank Test ◽  
De Novo Mutations ◽  
Cardiac Morbidity ◽  
Danon Disease

Abstract Background Danon Disease (DD) is a rare X-linked autophagic vacuolar myopathy, characterized by high penetrance and severe cardiomyopathy; cognitive, skeletal muscle and vision impairment may occur as well. Due to its rarity, clinical presentation and outcomes are still uncertain. Purpose To describe clinical features and outcomes of DD in female and male patients Methods Individuals and families from United Kingdom, Australia, and United States were recruited through via advertisements on Facebook groups related to DD. Participants completed a survey about symptoms and medical history and provided their medical records to the research team. Results A total of 44 patients (54.5% female) with positive genetic testing for DD were included. De novo mutations occurred in one out of four patients. Cardiomyopathy occurred in 86.3% of patients (18/24 females, 20/20 males) at a mean age of 7.3 years for males and 19.4 years for females (p=0.001). Females presented with either hypertrophic cardiomyopathy (HCM, 66.7%) or dilated cardiomyopathy (DCM, 8.3%) whereas males presented with HCM 90% of the time. 34.2% of patients were diagnosed with Wolff-Parkinson-White syndrome. Twelve patients (7 females, 5 males) underwent cardiac magnetic resonance (CMR) Out of the 9 cases, 8 (88.9%) exhibited extensive patchy late gadolinium-enhancement (LGE) in multiple segments of the left ventricle; 3 cases also had right ventricular LGE. Median cardiac mass index was 155 g/m2 (Q1-Q3: 70–237; v.n. 31–79 g/m2). Overall, 17 (38.6%) patients died or required or heart transplant (HTx). Median age at the time of death or HTx was 17 years and 42 years in males and females, respectively (p=0.025 by the log-rank test) Cognitive impairment, mainly described as learning disabilities, was diagnosed in 90.0% of males (18/20) and 79.2% (19/24) of females; intelligence quotient (IQ) measurement was reported in 8 patients (3 females, 5 males) and 7 of them showed IQ below the average. Symptomatic skeletal myopathy was present in 28 (63.3%) of patients, with a higher prevalence in males (85% vs. 45.8%; p<0.01). Retinopathy was reported in 14 (31.2%) patients and occurred equally in both genders (p=0.34). Conclusions DD causes significant cardiac morbidity with the need for transplant at a young age; in 25% of cases DD is due to a de novo mutation. While in males DD is more frequently multisystemic with a more rapid clinical deterioration, in females the clinical presentation is variable. However, the presence of severe cases in females warrant the clinicians to screen for DD in both sexes with clinical manifestations or positive family history Acknowledgement/Funding Rocket Pharmaceuticals

scholarly journals Analysis of De Novo Mutations in Sporadic Cardiomyopathies Emphasizes Their Clinical Relevance and Points to Novel Candidate Genes

2020 ◽  
Vol 9 (2) ◽  
pp. 370 ◽  
Author(s):  
Maria Franaszczyk ◽  
Grazyna Truszkowska ◽  
Przemyslaw Chmielewski ◽  
Malgorzata Rydzanicz ◽  
Joanna Kosinska ◽  
...  
Keyword(s):  
Candidate Genes ◽  
De Novo ◽  
Positive Family History ◽  
Disease Onset ◽  
De Novo Mutation ◽  
De Novo Mutations ◽  
Whole Exome ◽  
The Family ◽  
High Prevalence ◽  
Generation Sequencing

The vast majority of cardiomyopathies have an autosomal dominant inheritance; hence, genetic testing is typically offered to patients with a positive family history. A de novo mutation is a new germline mutation not inherited from either parent. The purpose of our study was to search for de novo mutations in patients with cardiomyopathy and no evidence of the disease in the family. Using next-generation sequencing, we analyzed cardiomyopathy genes in 12 probands. In 8 (66.7%), we found de novo variants in known cardiomyopathy genes (TTN, DSP, SCN5A, TNNC1, TPM1, CRYAB, MYH7). In the remaining probands, the analysis was extended to whole exome sequencing in a trio (proband and parents). We found de novo variants in genes that, so far, were not associated with any disease (TRIB3, SLC2A6), a possible disease-causing biallelic genotype (APOBEC gene family), and a de novo mosaic variant without strong evidence of pathogenicity (UNC45A). The high prevalence of de novo mutations emphasizes that genetic screening is also indicated in cases of sporadic cardiomyopathy. Moreover, we have identified novel cardiomyopathy candidate genes that are likely to affect immunological function and/or reaction to stress that could be especially relevant in patients with disease onset associated with infection/infestation.

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