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C Mutation (c + mutation)
Selected AbstractsCompound heterozygosity of two missense mutations in the NADH-cytochrome b5 reductase gene of a Polish patient with type I recessive congenital methaemoglobinaemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2003Dorota Grabowska Abstract: A case of type I methaemoglobinaemia observed in a Polish subject with compound heterozygosity for two mutations in the reduced nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase (b5R) gene is described. One is a novel mutation 647T,C which leads to substitution of isoleucine by threonine at position 215 (I215T). This maternal mutation was found in several family members. A previously known mutation, 757G,A, leads to the replacement of valine by methionine at position 252 (V252M). The latter mutation was found also in the father and one of the two brothers. The effects of these mutations were analysed on a model of the human b5R protein obtained by homology modelling. Although both amino acid substitutions are located in the NADH-binding domain, the whole protein structure, especially the region between the flavin adenine dinucleotide and NADH-binding domains, is disturbed. The structural changes in the I215T mutant are less prominent than those in the V252M mutant. We presume that the 647T,C mutation is a type I mutation, however, it has not been observed in the homozygous state. [source] Chediak-Higashi syndrome mutation and genetic testing in Japanese black cattle (Wagyu)ANIMAL GENETICS, Issue 1 2000H Yamakuchi Summary Chediak-Higashi Syndrome (CHS) is an autosomal recessive disorder that affects several species including mice, humans, and cattle. Evidence based on clinical characteristics and somatic cell genetics suggests that mutations in a common gene cause CHS in the three species. The CHS locus on human chromosome 1 and mouse chromosome 13 encodes a lysosomal trafficking regulator formerly known as LYST, now known as CHS1, and is defective in CHS patients and beige mice, respectively. We have mapped the CHS locus to the proximal region of bovine chromosome 28 by linkage analysis using microsatellite markers previously mapped to this chromosome. Furthermore, we have identified a missense A:T,G:C mutation that results in replacement of a histidine with an arginine residue at codon 2015 of the CHS1 gene. This mutation is the most likely cause of CHS in Wagyu cattle. In addition, we describe quick, inexpensive, PCR based tests that will permit elimination of the CHS mutation from Wagyu breeding herds. [source] Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith,Lemli,Opitz syndromeANNALS OF HUMAN GENETICS, Issue 3 2001P. E. JIRA Smith,Lemli,Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7-dehydrocholesterol reductase (DHCR7; EC 1.3.1.21), the final enzyme of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor 7-dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency of the previously described IVS8,1 G > C splice acceptor site mutation (two homozygotes, eight compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were detected in eleven patients with a mild to moderate SLOS-phenotype. The mutations include three novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation (IVS8,1 G > T). Two patients, homozygous for the IVS8,1 G > C mutation, presented with a severe clinical phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS-phenotype disclosed compound heterozygosity of the IVS8,1 G > C mutation in combination with different novel and known missense mutations. [source] A novel RAB7 mutation associated with ulcero-mutilating neuropathyANNALS OF NEUROLOGY, Issue 4 2004Henry Houlden PhD, MRCP There are two known autosomal dominant genes for the hereditary ulcero-mutilating neuropathies: SPTLC1 (hereditary sensory neuropathy type 1) and RAB7 (Charcot,Marie,Tooth disease type 2B). We report a family with autosomal dominant ulcero-mutilating neuropathy, developing in the teens and characterized by ulcers, amputations, sensory involvement in the feet but no motor features. Sequencing the RAB7 gene showed a novel heterozygous A to C mutation, changing asparagine to threonine at codon 161. The mutation is situated adjacent to a previously identified valine to methionine mutation at codon 162, implying a hotspot for mutations in the highly conserved C terminus of RAB7. Ann Neurol 2004;56:586,590 [source] A novel mutation in the mitochondrial tRNA for tryptophan causing a late-onset mitochondrial encephalomyopathyACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010P. S. Sanaker Sanaker PS, Nakkestad HL, Downham E, Bindoff LA. A novel mutation in the mitochondrial tRNA for tryptophan causing a late-onset mitochondrial encephalomyopathy. Acta Neurol Scand: 2010: 121: 109,113. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background,,, Mitochondrial DNA (mtDNA) mutations are increasingly being recognized as causes of late-onset disease. We report a patient with a late-onset mitochondrial encephalomyopathy caused by a novel G > C transition in mtDNA at position 5556 in the gene encoding the tRNA for tryptophan (MTTW). Aims,,, To investigate the cause of disease and assess the pathogenicity of this new mutation. Methods,,, Clinical, histopathological and gene sequencing studies. Quantification of the mutation was performed in different tissues from the patient and two relatives and in single muscle fibres. Results,,, The mutation was heteroplasmic, segregated in biochemically affected muscle fibres and was absent in blood. The level of mutation in skeletal muscle was higher than in brain, although the brain was clinically the most affected tissue. Discussion,,, The 5556G > C mutation appears sporadic. It was not found in any of the family members tested, although some of them manifested disorders that can be associated with mtDNA disease. In addition to reporting the eighth mutation in MTTW, our case illustrates the challenges posed when assigning pathogenicity to mtDNA mutations. [source] C/EBPA gene mutation and C/EBPA promoter hypermethylation in acute myeloid leukemia with normal cytogenetics,,AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2010Ying Lu In the current study, we investigated C/EBPA gene mutations and promoter hypermethylation in a series of 53 patients with CN-AML. In addition, we also analyzed two other frequent mutations (FLT3/ITD and NPM1) in these patients and correlated them with C/EBPA gene alterations. 13/53 patients were FLT3/ITD+/NPM1- , 11/53 patients were FLT3/ITD+/NPM1+, 9/53 patients were FLT3/ITD-/NPM1+, and 20/53 patients were FLT3/ITD-/NPM1- . Four of 53 cases displayed C/EBPA mutations, whereas 49 cases had only C/EBPA wild-type alleles. Of the four positive cases, three patients had N-terminal mutations only, whereas one patient had mutations in both the N- and C-terminal region. Two of the four positive cases also harbored both FLT3/ITD and NPM1 mutation simultaneously, whereas the other two patients had neither FLT3/ITD nor NPM1 mutations. Furthermore, 7/53 cases displayed C/EBPA promoter hypermethylation. Interestingly, they were all in CN-AML cases without FLT3/ITD or NPM1 mutations. None of the seven patients with C/EBPA promoter hypermethylation showed C/EBPA mutation. In conclusion, C/EBPA mutation and promoter hypermethylation can be detected at a relatively low frequency in de novo CN-AML patients, suggesting they may contribute to leukemogenesis. C/EBPA mutation appears to be seen in "high-risk" AML (FLT3/ITD+/NPM1+; FLT3/ITD+/NPM1- or FLT3/ITD-/NPM1- ), while C/EBPA hypermethylation appears to be more common in AML with FLT3/ITD - /NPM1 - and is not associated with C/EBPA mutation. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Evidence for allelic evolution of C/EBPalpha mutations in acute myeloid leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2003Jens Tiesmeier Summary. Transcription factor CCAAT/enhancer binding protein , (C/EBP,) is mutated in 6,10% of patients with acute myeloid leukaemia (AML). Recently, we reported the emergence of an N-terminal C/EBP, mutation after chemotherapy in a patient with secondary AML. The clone carrying the mutation became the dominant clone at relapse. This observation prompted us to compare the C/EBP, mutational status of 26 de novo non-core binding factor AML patients at diagnosis and at relapse after induction and consolidation chemotherapy. Four mutations in the C/EBP, gene were identified in two out of 26 patients. In both these cases, a biallelic mutation was present at diagnosis and at relapse: an amino-terminal frameshift mutation and a mutation of the fork/leucine finger 1 region. In patient 1, the amino-terminal frameshift mutation was duplicated and found on both alleles at relapse. In patient 2, the amino-terminal frameshift mutation and a mutation in the fork region were found either alone or combined on the same allele, suggesting a subclone formation. None of the patients without a C/EBP, mutation at diagnosis showed a mutation at relapse. This is the first report of an evolution of the C/EBP, gene between diagnosis and relapse in AML. [source] | |||||||||||||||||||||||||