Abstract
Mitochondrial DNA (mtDNA) defects were known to be associated with a large spectrum of human diseases and patients might present wide range of clinical features with various combinations. ...Mutations in mitochondrial tRNAs, rRNAs and protein-coding genes or large-scale rearrangements have been implicated in several cytopathies. Mitochondrial myopathies, usually maternally inherited group of neuromuscular diseases caused by mitochondrial dysfunction occurring before the age of 20 years and often begin with exercise intolerance, muscle weakness and neurodevelopmental retardation. We studied the mtDNA in three Tunisian patients with mitochondrial myopathy. The mutational analysis screening revealed the presence of two mitochondrial mutations: the m.5521G > A mutation in the D-stem region of the tRNATrp gene which could lead to a disruption of the secondary structure of this tRNA and affect the tRNA-ribosome interaction with a consequent decrease in the rate of synthesis of mitochondrial proteins. The second mutation is the m.8249G > A (p.G222R) variation in the MT-CO2 gene which may affect the electrons transfer from cytochrome c to the bimetallic center of the catalytic subunit I.
To investigate the spectrum of common mitochondrial mutations in Tunisia during the years of 2002-2012, 226 patients with mitochondrial disorders were clinically diagnosed with hearing loss, Leigh ...syndrome (LS), diabetes, cardiomyopathy, Kearns-Sayre syndrome (KSS), Pearson syndrome (PS), myopathy, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) and Wolfram syndrome. Restriction fragment length polymorphism (PCR-RFLP), radioactive PCR, single specific primer-PCR (SSP-PCR) analysis and PCR-sequencing methods were used to identify the mutations. Two cases with m.1555A>G mutation and two families with the novel 12S rRNA m.735A>G transition were detected in patients with hearing loss. Three cases with m.8993T>G mutation, two patients with the novel m.5523T>G and m.5559A>G mutations in the tRNATrp gene, and two individuals with the undescribed m.9478T>C mutation in the cytochrome c oxidase subunit III (COXIII) gene were found with LS. In addition, one case with hypertrophic cardiomyopathy and deafness presented the ND1 m.3395A>G mutation and the tRNAIle m.4316A>G variation. Besides, multiple mitochondrial deletions were detected in patients with KSS, PS, and Wolfram syndrome. The m.14709T>C mutation in the tRNAGlu was reported in four maternally inherited diabetes and deafness patients and a novel tRNAVal m.1640A>G mutation was detected in a MELAS patient.
BACKGROUNDPeters Plus syndrome (MIM 261540) is a rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor abnormalities. Mutations ...in the B3GALTL gene encoding the β-1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. CASE PRESENTATIONWe report here a female patient with severe manifestations of Peters Plus syndrome including facial dysmorphism and bilateral corneal opacity associated with left renal pyelo-calicial dilatation and sexual ambiguity. Total sequencing of the B3GALTL gene revealed no mutation in the patient. CONCLUSIONTo our knowledge, sexual ambiguity has not previously been reported in Peters Plus syndrome so far, and renal malformation is also apparently rare in the syndrome.
The genetic origin of Rheumatoid Arthritis (RA) is largely unknown. The purpose of this investigation was to assess the potential genetically determined involvement of the immunoglobulin (Ig) heavy ...chain variable region (VH) locus in the pathogenesis of RA. We tested the hypothesis of whether there is a genetic linkage between a structural abnormality of the VH gene complex and autoantibody hyperproduction in RA. We used restriction endonuclease generated polymorphism with human VH gene-family-specific probes to examine genomic DNA from a RA family and from unrelated RA patients from both the Tunisian and the European populations. The use of DNA samples from these ethnic origins permitted a further evaluation of the polymorphism of the human VH locus. While we found that the polymorphism of the VH locus was lower in the Tunisian population, we could not detect a restriction site polymorphism pattern restricted to RA. Together, our results do not support the involvement of major abnormalities of the Ig VH locus as a primary source in the development of RA.
Human alpha heavy chain disease is characterized by the production of abnormally short alpha IgH chains. In previously published cases it has been found that the malignant cells produce abnormal ...alpha mRNA, lacking VH and CH1 sequences and composed of a leader sequence peptide, sequences of variable length (69 to 84 bp) and of unknown origin, followed by normal CH2 and CH3 sequences. In this study we established the nucleotide sequence of alpha mRNA for six cases of alpha heavy chain disease. We observed that all six alpha mRNA lack the VH and CH1 sequences as do those previously described. They also contain in-frame inserts of unknown origin between the leader peptide and the normal CH2 and CH3 coding sequences. These inserts are of variable length (42 to 105 bp) and they are unrelated. These results suggest the existence of a common mechanism defect leading to deletions/insertions in alpha heavy chain disease rather than a specific interaction between alpha 1 IgH gene with a unique defined molecular species.
