Structural analysis of missense mutations in galactokinase 1 (GALK1) leading to galactosemia type-2

2018 ◽  
Vol 119 (9) ◽  
pp. 7585-7598 ◽  
Author(s):  
Sneha P ◽  
Elaheh Ahmad Ebrahimi ◽  
Sara Ahmed Ghazala ◽  
Thirumal Kumar D ◽  
Siva R ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Missense Mutations

Structural analysis of tooth and jawbone in a type 2 diabetes mouse model

2014 ◽  
Author(s):  
Silvia Pabisch ◽  
Tsuguno Yamaguchi ◽  
Yasushi Koike ◽  
Kenji Egashira ◽  
Shinsuke Kataoka ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Structural Analysis ◽  
Mouse Model ◽  
Diabetes Mouse

Pitt–Hopkins syndrome: phenotypic and genotypic description of four unrelated patients and structural analysis of corresponding missense mutations

Neurogenetics ◽  
2021 ◽  
Author(s):  
Tingting Zhao ◽  
Georgi Z. Genchev ◽  
Shengnan Wu ◽  
Guangjun Yu ◽  
Hui Lu ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Missense Mutations

scholarly journals Missense mutations in theTGM2 gene encoding transglutaminase 2 are found in patients with early-onset type 2 diabetes

2007 ◽  
Vol 28 (11) ◽  
pp. 1150-1150 ◽  
Author(s):  
O. Porzio ◽  
O. Massa ◽  
V. Cunsolo ◽  
C. Colombo ◽  
M. Malaponti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Early Onset ◽  
Transglutaminase 2 ◽  
Missense Mutations ◽  
Gene Encoding ◽  
Onset Type

scholarly journals Structural analysis of pathogenic missense mutations in GABRA2 and identification of a novel de novo variant in the desensitization gate

2020 ◽  
Vol 8 (7) ◽  
Author(s):  
Alba Sanchis‐Juan ◽  
Marcia A. Hasenahuer ◽  
James A. Baker ◽  
Amy McTague ◽  
Katy Barwick ◽  
...  
Keyword(s):  
Structural Analysis ◽  
De Novo ◽  
Missense Mutations ◽  
De Novo Variant

scholarly journals Novel genotype–phenotype correlations in five Chinese families with Von Hippel–Lindau disease

2018 ◽  
Vol 7 (7) ◽  
pp. 870-878 ◽  
Author(s):  
Qiuli Liu ◽  
Gang Yuan ◽  
Dali Tong ◽  
Gaolei Liu ◽  
Yuting Yi ◽  
...  
Keyword(s):  
Malignant Neoplasms ◽  
Missense Mutations ◽  
Chinese Families ◽  
Von Hippel Lindau ◽  
Disease Phenotypes ◽  
Mri Scans ◽  
Von Hippel Lindau Disease ◽  
Vhl Disease

Context Von Hippel–Lindau (VHL) disease manifests as a variety of benign and malignant neoplasms. Previous studies of VHL disease have documented several genotype–phenotype correlations; however, many such correlations are still unknown. Increased identification of new mutations and patients with previously described mutations will allow us to better understand how VHL mutations influence disease phenotypes. Patients and design A total of 45 individuals from five unrelated families were evaluated, of which 21 patients were either diagnosed with VHL disease or showed strong evidence related to this disease. We compared the patients’ gene sequencing results with their medical records including CT or MRI scans, eye examinations and laboratory/pathological examinations. Patients were also interviewed to obtain information regarding their family history. Results We identified four missense mutations: c.239G>T (p.Ser80Ile), linked with VHL Type 2B, was associated with renal cell carcinoma, pheochromocytoma and hemangioma in the cerebellum; c.232A>T (p.Asn78Tyr) manifested as RCC alone and likely caused VHL Type 1; c.500G>A (p.Arg167Gln) mutation was more likely to cause VHL Type 2 than Type 1 as it preferentially induced Pheo and HB in the retina, cerebellum and spinal cord; c.293A>G (p.Try98Cys) was associated with Pheo and thus likely induced VHL Type 2. Conclusions Characterizing VHL disease genotype–phenotype correlations can enhance the ability to predict the risk of individual patients developing different VHL-related phenotypes. Ultimately, such insight will improve the diagnostics, surveillance and treatment of VHL patients. Precis Four missense mutations in VHL have been identified in 21 individuals when five unrelated Chinese families with VHL disease were analyzed; VHL mutations are highly associated with unique disease phenotypes.

Update of the spectrum of mucopolysaccharidoses type III in Tunisia: identification of three novel mutations and in silico structural analysis of the missense mutations

2017 ◽  
Vol 13 (4) ◽  
pp. 374-380 ◽  
Author(s):  
Souad Ouesleti ◽  
Maria Francisca Coutinho ◽  
Isaura Ribeiro ◽  
Abdehedi Miled ◽  
Dalila Saidane Mosbahi ◽  
...  
Keyword(s):  
Structural Analysis ◽  
In Silico ◽  
Missense Mutations ◽  
Novel Mutations ◽  
Type Iii

Structural analysis of human glutamine:fructose-6-phosphate amidotransferase, a key regulator in type 2 diabetes

FEBS Letters ◽  
2008 ◽  
Vol 583 (1) ◽  
pp. 163-167 ◽  
Author(s):  
Yuichiro Nakaishi ◽  
Masahiko Bando ◽  
Hiroshi Shimizu ◽  
Kenji Watanabe ◽  
Fumitaka Goto ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Structural Analysis

MUNC13–4 Mutations in Patients with Hemophagocytic Lymphohistiocytosis Are Scattered over the Functional Domains of the Protein.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1249-1249
Author(s):  
Alessandra Santoro ◽  
Sonia Cannella ◽  
Giovanna Bossi ◽  
Federico Gallo ◽  
Antonino Trizzino ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Stop Codon ◽  
Functional Domains ◽  
Functional Domain ◽  
Missense Mutations ◽  
Coding Region ◽  
Cycle Sequencing ◽  
Familial Form ◽  
Protein Functional Domains

Abstract Mutations of PRF1 and MUNC13–4 genes, involved with cellular cytotoxicity, are associated with the familial form of Hemophagocytic Lymphohistiocytosis (HLH) type 2 (FHL2) and 3 (FHL3). In all patients with HLH, in which PRF1 mutations had been excluded, we screened MUNC13–4 mutations. The 32 exons and their proximal flanking regions of MUNC13–4 gene were sequenced by “cycle sequencing” approach (BigDye Terminator, Applied Biosystems). Of 60 patients, 21 had MUNC13–4 mutations. 5 were reported mutations: 753+1G>T, 817C>T (R273X); 1389+1G>A; 1822del 12 bp (del V608-A611); 2346–9delGGAG (R782FsX12). Of 16 novel mutations 2 (2212C>T and 2650C>T) introduce a stop codon (at Q738 and Q884); 4 cause frameshift: 441delA (P147fsX14), 532delC (Q178fsX70), 3082delC (L1028fsX), and 3226insG (H1076fsX51). Of 8 missense mutations [175G>A (A59T), 419T>C (I140T), 610A>G (M204B), 1241G>T (R414L), 1847A>G (E616G), 2039G>C (R680P), 2570T>G (F857C), 2782C>T (R928C)], 6 fall within the protein functional domains; each of the 2 falling outside was associated with 2 additional pathogenic mutations. The remaining novel 1992+5 G>A and 2448insC −12 fall outside the coding region but are close enough to induce alternative splicing. We identified polymorphisms 279C>T and 3198A>G. The 2599A>G (K867E) transition was found in several unrelated families, including one homozygous parent. To assess its frequency we studied 50 consecutive newborns, of which 64% were heterozygous. To understand the effects of the mutations we analysed Munc13–4 protein expression from CTL and/or NK cells by western blot using an antibody raised against amino acids 1–262. Trace amounts of protein could be detected only in 5 patients. Analysis of granule polarisation in 2 patients with trace amounts of Munc13–4 protein showed many more docked granules visible than in controls, consistent with a block in granule secretion in these patients. Median age at diagnosis of FHL3 was 6.5 months, but 8/21 (38%) patients were diagnosed when older than 5 years, with one young adult of 18 years. CNS disease was present in 10 patients; NK was markedly reduced or absent in all patients tested. MUNC13–4 mutations were found in 35% of our HLH patients non type-2. Mutations were almost entirely different from those reported so far and scattered over different exons, but in far most cases they fall within the protein functional domain. Since these patients may develop the disease during adolescence or even later on, not only pediatric but also as adults hematologists should include FHL-2 and 3 in the differential diagnosis of children and young adults with fever, cytopenia, splenomegaly and hypercytokinemia.

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