In silico analysis of novel mutations in maple syrup urine disease patients from Iran

2016 ◽  
Vol 32 (1) ◽  
pp. 105-113 ◽  
Author(s):  
Maryam Abiri ◽  
Razieh Karamzadeh ◽  
Marziyeh Mojbafan ◽  
Mohammad Reza Alaei ◽  
Atefeh Jodaki ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
In Silico ◽  
In Silico Analysis ◽  
Novel Mutations ◽  
Maple Syrup ◽  
Urine Disease ◽  
Silico Analysis

Neonatal maple syrup urine disease in China: two novel mutations in the BCKDHB gene and literature review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hong‐Hua Jiang ◽  
Yan Guo ◽  
Xian Shen ◽  
Ying Wang ◽  
Ting-Ting Dai ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Chinese Literature ◽  
Brain Mri ◽  
Classical Type ◽  
Novel Mutations ◽  
Maple Syrup ◽  
Gene Testing ◽  
Urine Disease ◽  
Bckdhb Gene ◽  
Branched Chain

Abstract Objectives To report two novel mutations in the BCKDHB gene with Maple syrup urine disease (MSUD) and compare their data with 52 cases of MSUD reported in the available Chinese literature. Methods Clinical data of a case of a newborn with MSUD was retrospectively studied. Literatures on MSUD in the local medical journals from January 1990 till December 2019 in China were reviewed. Results Two novel BCKDHB mutations c.90_91insCTGGCGCGGGG (p.Phe35TrpfsTer41) and c.80_90del (p.Ala32PhefsTer48) were identified. We found a total of 52 cases of MSUD reports so far. A total of 49 cases had the symptom of poor feeding (94.2%), 50 cases showed poor responses to stimulation (96.2%), 21 cases had odor of maple syrup (40.3%), 29 cases had seizures (55.7%), and 13 cases had respiratory failure (25.0%). The average of the blood ammonia was 127.2 ± 75.0 μmol/L. A total of 18 cases reported the gene testing, among of them 9 cases of BCKDHA mutations, 6 cases of BCKDHB mutations, and 2 cases of DBT mutations. A total of 13 cases (25%) were treated with mechanical ventilation, 50 cases (96.2%) with protein-restricted diet and l-carnitine, 29 cases with thiamine, and only 2 cases were treated with blood purification. Finally, 19 patients (36.5%) were died, 21 cases (40.4%) were improved after treatments. Conclusions The clinical phenotype of neonatal MSUD in China belongs to the classical type currently. Suspected patients should have blood or urine branched-chain amino acid levels tested and brain MRI as early as possible to enable early diagnosis, thus improvement in prognosis.

Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jianmei Yang ◽  
Jianjun Xiu ◽  
Yan Sun ◽  
Fan Liu ◽  
Xiaohong Shang ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Structural Changes ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Novel Mutations ◽  
Metabolic Encephalopathy ◽  
Maple Syrup ◽  
Feeding Difficulties ◽  
Urine Disease ◽  
The Impact

Abstract Background Maple syrup urine disease (MSUD) is a rare metabolic autosomal recessive disorder caused by deficiency of the branched-chain α-ketoacid dehydrogenase complex. Mutations in the BCKDHA, BCKDHB and DBT genes are responsible for MSUD. This study presents the clinical and molecular characterizations of four MSUD patients. Methods Clinical data of patients were retrospectively analyzed, and genetic mutations were identified by whole-exome sequencing. CLUSTALX was employed to analyzed cross-species conservation of the mutant amino acid. The impact of the mutations was analyzed with PolyPhen-2 software. The I-TASSER website and PyMOL software were used to predict the protein three-position structure of the novel mutations carried by the patients. Results Vomiting, irritability, feeding difficulties, seizures, dyspnoea, lethargy and coma were the main clinical presentations of MSUD. Cranial MRI showed abnormal symmetrical signals in accordance with the presentation of inherited metabolic encephalopathy. Seven mutations were detected in four patients, including three novel pathogenic mutations in the BCKDHA (c.656C>A), BCKDHB (deletion of a single-copy of BCKDHB) and DBT (c.1219dup) genes. Structural changes were compatible with the observed phenotypes. Conclusions Different types of MSUD can display heterogeneous clinical manifestations. Exhaustive molecular studies are necessary for a proper differential diagnosis. The newly identified mutation will play a key role in the prenatal diagnosis of MSUD in the future.

scholarly journals Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease

2003 ◽  
Vol 22 (5) ◽  
pp. 417-417 ◽  
Author(s):  
Marco Henneke ◽  
Nadine Flaschker ◽  
Christoph Helbling ◽  
Martina Müller ◽  
Peter Schadewaldt ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Novel Mutations ◽  
Maple Syrup ◽  
Urine Disease

Identification of eight novel mutations in 11 Chinese patients with maple syrup urine disease

2020 ◽  
Vol 16 (4) ◽  
pp. 401-410 ◽  
Author(s):  
Wei-Hua Sun ◽  
Bing-Bing Wu ◽  
Ya-Qiong Wang ◽  
Meng-Yuan Wu ◽  
Xin-Ran Dong ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Chinese Patients ◽  
Novel Mutations ◽  
Maple Syrup ◽  
Urine Disease

Maple syrup urine disease mutation spectrum in a cohort of 40 consanguineous patients and insilico analysis of novel mutations

2019 ◽  
Vol 34 (4) ◽  
pp. 1145-1156 ◽  
Author(s):  
Maryam Abiri ◽  
Hassan Saei ◽  
Maryam Eghbali ◽  
Razieh Karamzadeh ◽  
Tina Shirzadeh ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Mutation Spectrum ◽  
Novel Mutations ◽  
Maple Syrup ◽  
Disease Mutation ◽  
Urine Disease

Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease

2018 ◽  
Vol 31 (2) ◽  
pp. 205-212 ◽  
Author(s):  
Monica Zeynalzadeh ◽  
Alireza Tafazoli ◽  
Azadeh Aarabi ◽  
Morteza Moghaddassian ◽  
Farah Ashrafzadeh ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Energy Levels ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Strong Correlations ◽  
Novel Mutations ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase

Abstract Background: Maple syrup urine disease (MSUD) is a rare metabolic autosomal recessive disorder caused by dysfunction of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex. Mutations in the BCKDHA, BCKDHB and DBT genes are responsible for MSUD. The current study analyzed seven Iranian MSUD patients genetically and explored probable correlations between their genotype and phenotype. Methods: The panel of genes, including BCKDHA, BCKDHB and DBT, was evaluated, using routine the polymerase chain reaction (PCR)-sequencing method. In addition, protein modeling (homology and threading modeling) of the deduced novel mutations was performed. The resulting structures were then analyzed, using state-of-the-art bioinformatics tools to better understand the structural and functional effects caused by mutations. Results: Seven mutations were detected in seven patients, including four novel pathogenic mutations in BCKDHA (c.1198delA, c.629C>T), BCKDHB (c.652C>T) and DBT (c.1150A>G) genes. Molecular modeling of the novel mutations revealed clear changes in the molecular energy levels and stereochemical traits of the modeled proteins, which may be indicative of strong correlations with the functional modifications of the genes. Structural deficiencies were compatible with the observed phenotypes. Conclusions: Any type of MSUD can show heterogeneous clinical manifestations in different ethnic groups. Comprehensive molecular investigations would be necessary for differential diagnosis.

scholarly journals Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Ana Vitoria Barban Margutti ◽  
Wilson Araújo Silva ◽  
Daniel Fantozzi Garcia ◽  
Greice Andreotti de Molfetta ◽  
Adriana Aparecida Marques ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
In Silico Analysis ◽  
Cross Sectional Study ◽  
Clinical Severity ◽  
Cross Sectional ◽  
Maple Syrup ◽  
Molecular Features ◽  
Pathogenic Variants ◽  
Study Results ◽  
Urine Disease

Abstract Background Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. Results Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. Conclusion Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

scholarly journals In Silico Analysis of B3GALTL Gene Reveling 13 Novel Mutations Associated with Peters’-plus syndrome

2020 ◽  
Author(s):  
Abdelrahman H. Abdelmoneim ◽  
Arwa A. Satti ◽  
Miysaa I. Abdelmageed ◽  
Naseem S. Murshed ◽  
Nafisa M. Elfadol ◽  
...  
Keyword(s):  
In Silico ◽  
Autosomal Recessive ◽  
In Silico Analysis ◽  
Autosomal Recessive Disorder ◽  
Coding Region ◽  
Novel Mutations ◽  
Physiochemical Properties ◽  
Peters Anomaly ◽  
Systemic Manifestations ◽  
Silico Analysis

AbstractBackgroundPeters’-plus syndrome is a rare autosomal recessive disorder, which is characterized by a specific malformation of the eye that includes corneal opaqueness and iridocorneal adhesions (Peters’ anomaly) along with other systemic manifestations. Furthermore, various researches report the association between B3GALTL gene and Peters’-plus syndrome. In the current work we aim to analyze the deleterious SNPs in B3GALTL gene that predispose to Peters’-plus syndrome.Methodthe associated SNPs of the coding region of the B3GALTL gene was acquired from National Center for Biotechnology Information and then analyzed by eight softwares (SIFT, Polyphen2, Proven, SNAP2, SNP@GO, PMut, Imutant and Mupro). The physiochemical properties of the resulted SNPs were then analyzed by Hope project website and visualized by chimera software.ResultThirteen novel mutations (Y172C, A222V, C260R, C260Y, D349G, I354K, R377C, G379C, G393R, G393E, G395E, G425E, R445W) are discovered in B3GALTL gene to cause deleterious effects leading to the development of Peters’-plus syndrome.ConclusionThirteen novel mutations in B3GALTL gene are predicted to cause Peters’-plus syndrome.

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