Effect of Vasoactive Therapy Used for Brain-Dead Donors on Graft Survival After Kidney Transplantation.

Serum catecholamine levels and peripheral vascular resistance decrease after brain death. Vasoactive drugs are used to control these hemodynamic changes and to improve perfusion of the organs. These drugs might have a role in rejection or loss of the graft organ. We aimed to investigate the effects of vasoactive drugs used in the cadaveric donor care on post-transplant renal graft functions. In this retrospective study, medical records of 135 cadaveric donors (270 kidneys) and recipients of these kidneys were evaluated. Correlation analysis was done to assess the data for factors that may cause rejection and graft loss. Vasoactive drug (noradrenaline 49%, dopamine 60%, adrenaline 3%, dobutamine 11%) consumption ratio was 85.8% in donor care. Increased number of noradrenaline infusion days was associated with decreased rates of graft rejection and graft loss. This correlation was not found for dopamine. Results of the Pearson correlation analysis test showed a relation between noradrenaline use and decrease in graft loss and graft rejection. Noradrenaline but not dopamine used in cadaveric donor care decreased the graft rejection rate and graft loss, presumably by improving hemodynamic stability and organ perfusion, although we found no special reason.

Effect of Interviews Done by Intensive Care Physicians on Organ Donation.

In this study, we examined the correspondence between intensive care unit physicians and the relatives of potential brain-dead donors regarding the decision to donate or the reasons for refusing organ donation. A total of 12 consecutive cases of potential brain-dead patients treated in intensive care units of Marmara University Pendik Education and Research Hospital in 2013 were evaluated. For each of the cases, the Potential Donor Questionnaire, and Family Notification, Brain Death Criteria Fulfilment and Organ Donation Conversation Questionnaires were used to collect the required data. Statistically, descriptive analyses were performed. We concluded that honestly, regularly, and sufficiently informed relatives of the potential brain-dead donor more readily donate organs, with a positive contribution from the intensive care physician.

Beta-sarcoglycan gene mutations in Turkey.

The term limb-girdle muscular dystrophy (LGMD) refers to a group of muscular dystrophies that, at the outset, affect primarily the muscles of the hip and shoulder girdle. Limb-girdle muscular dystrophy is genetically heterogeneous comprising autosomal dominant (types LGMD 1A-1E) as well as autosomal recessive forms (types LGMD 2A-2J known). A subgroup among the autosomal recessive forms comprises the sarcoglycanopathies (LGMD2C-2F), caused by mutations in the gamma (gamma-SG), alpha (alpha-SG), beta (beta-SG) and delta (delta-SG) sarcoglycan genes, respectively. The sarcoglycans form the sarcoglycan complex, part of the dystrophin-associated glycoproteins. Mutations in the beta-SG gene causes LGMD2E. Disease severity, in this form, varies from mild to severe phenotypes depending on the individual mutation. Homozygous missense mutations in critical locations may result in the total absence of alpha-, beta- and gamma-sarcoglycan from the muscle membrane and a phenotype as severe as null mutations. In the present study, through screening 80 unrelated LGMD2 families, we identified 13 families with LGMD2E. Mutations in the beta-SG gene were identified in 12 patients from nine families. One of these patients carried a previously reported truncating mutation (Q11X), while the other 11 carried novel missense/rameshift mutations (M1L, V89M, I92T, I92S, 739insA), some of which were seen in more than one patient and may, therefore, be more common in the Turkish population.

A homozygous nonsense mutation in delta-sarcoglycan exon 3 in a case of LGMD2F.

We present the first Turkish family with delta-sarcoglycanopathy (LGMD2F). A novel truncating mutation (E93X) in exon 3 was identified in the gene. The index case showed a severe course and there was no cardiac involvement. LGMD2F seems to be rare in our population.

A cross section of autosomal recessive limb-girdle muscular dystrophies in 38 families.

Limb-girdle muscular dystrophies constitute a broad range of clinical and genetic entities. We have evaluated 38 autosomal recessive limb-girdle muscular dystrophy (LGMD2) families by linkage analysis for the known loci of LGMD2A-F and protein studies using immunofluorescence and western blotting of the sarcoglycan complex. One index case in each family was investigated thoroughly. The age of onset and the current ages were between 11/2 and 15 years and 6 and 36 years, respectively. The classification of families was as follows: calpainopathy 7, dysferlinopathy 3, alpha sarcoglycan deficiency 2, beta sarcoglycan deficiency 7, gamma sarcoglycan deficiency 5, delta sarcoglycan deficiency 1, and merosinopathy 2. There were two families showing an Emery-Dreifuss phenotype and nine showing no linkage to the LGMD2A-F loci, and they had preserved sarcoglycans. gamma sarcoglycan deficiency seems to be the most severe group as a whole, whereas dysferlinopathy is the mildest. Interfamilial variation was not uncommon. Cardiomyopathy was not present in any of the families. In sarcoglycan deficiencies, sarcoglycans other than the primary ones may also be considerably reduced; however, this may not be reflected in the phenotype. Many cases of primary gamma sarcoglycan deficiency showed normal or only mildly abnormal delta sarcoglycan staining.

DNA diagnostic tests in Xp21 dystrophy families for prenatal diagnosis.

Duchenne and Becker muscular dystrophies are X-linked genetic disorders characterized by dystrophin gene defects. We have studied 250 families with Duchenne and Becker muscular dystrophies (D/BMD) by molecular genetic methods since 1992. Nineteen exons of the dystrophin gene were analyzed for deletion. In families with no deletion, linkage analysis was performed to follow the inheritance of mutant alleles in the affected families. Twenty of these families requested prenatal diagnosis. Six mothers were found to be non-carriers (99% accuracy), thus fetuses were examined in the remaining 14. Two fetuses were affected and terminated. We report our experience and our current clinical practice in providing prenatal studies for D/BMD.

Prenatal diagnosis of limb-girdle muscular dystrophy type 2C.

After studies which have mapped the gamma-sarcoglycan deficient limb-girdle muscular dystrophy (LGMD2C) to chromosome 13q12 and recent identification of mutations within this gene, prenatal diagnosis has become possible. The deletion of exon 5 in the gamma-sarcoglycan gene was found in a consanguineous family and prenatal diagnosis was successfully provided. This is the first prenatal diagnosis of LGMD2C.

A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey.

Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a clinically and genetically heterogenous group of diseases involving at least six different loci. Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at LGMD2E (4q12), gamma-SG at LGMD2C (13q12), and delta-SG at LGMD2F (5q33-q34). The gene product at LGMD2B (2p13-p16) is still unknown and at least one other gene is still unmapped. We investigated 20 Turkish families (18 consanguineous) diagnosed as having LGMD2. Most of our patients had onset of symptoms before age 10. The phenotypes varied from severe to benign. We analyzed the SG complex by immunofluorescence and/or western blot. Genotyping was performed using markers defining the six known loci and the suspected genes were screened for mutations. Six of 17 index cases showed deficiency of the SG complex, by immunofluorescence and/or western blot. Seven cases involved one of the known genes of the SG complex (alpha, 2; beta, 1; and gamma, 4 cases), and five mutations were documented in the alpha- and gamma-SG genes. After linkage analysis, 10 families were characterized as having LGMD2A (calpain-3 deficiency), and all mutations were eventually identified. One family was classified as having LGMD2B and 1 family that has normal SGs was linked to the chromosome 5q33-q34 locus (LGMD2F). In 1 family there was no linkage to any of the known LGMD2 loci. It appears that in Turkey, there is a broad spectrum of genes and defects involved in LGMD2. It may be possible to correlate genotype to phenotype in LGMD2. All severe cases belonged to the gamma-SG-deficiency group. Nine calpain-3-deficient cases had intermediate and 1 had moderate clinical courses. The LGMD2B patient had a moderate clinical expression, whereas the LGMD2F case was truly benign.

Calpain-3 deficiency causes a mild muscular dystrophy in childhood.

Among our 20 families with LGMD2, 10 were documented to have muscle-specific calcium-activated neutral protease 3 (calpain-3) deficiency. Consanguinity was present in all. The current ages of the index cases were between 12 and 23 years, and there were additional nine members affected. Clinically, the patients showed mild courses; none of the cases below age 30 lost autonomy so far. The dystrophy is mainly proximal and atrophic with calf enlargement and scapular wasting in some. In three cases walking was delayed. Creatine kinase levels were at least 10 times elevated. All obligate carriers had normal creatine kinase levels. Five families shared the same 551 delA frameshift mutation. In four of these families there was the same core haplotype, whereas one was distinct suggesting an independent origin. Calpain-3 deficiency in general is a mild muscular dystrophy during childhood.

Correlation of laboratory and clinical findings with the location of Xp21 deletion in Duchenne muscular dystrophy.

Laboratory and clinical features of 28 Duchenne muscular dystrophy patients were evaluated. Positive family history was present in only two cases (7.1%). Dystrophin I-positive fibers were present in 33 percent of the cases with the deletion close to the 5' end of the gene. In the cases with deletion concerning the central part of the gene, all fibers were dystrophin I-negative. In five of the six cases with short stature, the deletion was close to the 5' end of the gene, and short stature was especially seen together with 8th and 13th exon deletion. Statistical analysis concerning the age at which the patient began to have difficulty in standing up and at which he could not walk, did not correlate with the clinical severity and deletion zone, location or extent.

Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.

Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of the segregation of markers flanking the LGMD2A locus and a search for CANP3 mutations were performed for 21 LGMD2 pedigrees from various origins. In addition to the 16 mutations described previously, we report 19 novel mutations. These data indicate that muscular dystrophy caused by mutations in CANP3 are found in patients from all countries examined so far and further support the wide heterogeneity of molecular defects in this rare disease.

Identification of muscle-specific calpain and beta-sarcoglycan genes in progressive autosomal recessive muscular dystrophies.

The autosomal recessive forms of limb-girdle muscular dystrophies are encoded by at least five distinct genes. The work performed towards the identification of two of these is summarized in this report. This success illustrates the growing importance of genetics in modern nosology.

Molecular deletion patterns in Turkish Duchenne and Becker muscular dystrophy patients.

The dystrophin gene deletion patterns of Duchenne/Becker dystrophy were investigated in 57 DMD, 7 BMD and 1 DMD-BMD intermediate muscular dystrophy patients. Deletions, analyzed by multiplex amplification of selected exons, were observed in 58% (38 cases) of the patients. It was found that exon 48 was the most frequently affected, while exon 44 was the least frequently affected. The number of deleted exons was variable, but single exon deletions were more frequent (41%) than larger deletions in our population and the great majority of deletions began distal to exon 44. The application of PCR to deletion analysis in D/BMD was found to be very useful in delineating the extent of the deletion in most of the cases (82%). It was seen that the frequency of deletion breakpoints in distal part of the dystrophin gene (exons 42-52) was detected in 64% of our cases. In our group, the frequency of deletion breakpoints in the same area of the dystrophin gene was between that of the French and the Finnish patients. The distribution of deletion breakpoints within the dystrophin gene of the Turkish population seems to have some differences from other populations. Deletion breakpoints were found to be clustered mainly in three separate regions covering introns 44, 45 and 50 within the central region of the dystrophin gene. Intron 44 was mostly 5' breakpoints but it was found not to be involved as 3' breakpoints. The correlation between phenotype and type of deletion agreed with the reading frame theory except for one DMD case.

An unusual case of Duchenne muscular dystrophy.

A 10-year-old boy with Duchenne muscular dystrophy (DMD), with quite unusual clinical data, is presented. He was unable to walk until age 6, walked only for 9 months and then became wheel-chair bound. No dystrophin was present on muscle biopsy sections and a large deletion was found in the dystrophin gene. The deletion encompassed the central high frequency deletion region of the gene. Early developmental milestones may be delayed in DMD, but patients usually start to walk around 2-3 years of age. A delay of the extent in this case is very unusual.