scholarly journals Dystrophin gene mutations in two different ethnic families in Azerbaijan Republic

2020 ◽  
Vol 3 ◽  
pp. 157-163
Author(s):  
S. A. Aghayeva ◽  
◽  
A. M. Mammadov ◽  
N. A. Badalova ◽  
Keyword(s):  
Prenatal Diagnosis ◽  
Ethnic Groups ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Index Patient ◽  
Reproductive Age ◽  
Muscle Dystrophy ◽  
Genetical Analysis

Two different mutations: deletion of 13 exons (from 8th to 20th exons) in one index patient and deletion of 45th exon in the second one were identified by molecular genetical analysis for patients with Duchenne muscle dystrophy diagnosis from different ethnic groups, residing in Azerbaijan. Taking into account reproductive age of parents, the prenatal diagnosis of fetus is recommended for the following pregnancies.

scholarly journals Sensitivity and Frequencies of Dystrophin Gene Mutations in Thai DMD/BMD Patients As Detected by Multiplex PCR

2008 ◽  
Vol 25 (2) ◽  
pp. 115-121 ◽  
Author(s):  
Thanyachai Sura ◽  
Jakris Eu-ahsunthornwattana ◽  
Sarinee Pingsuthiwong ◽  
Manisa Busabaratana
Keyword(s):  
Muscular Dystrophy ◽  
Multiplex Pcr ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Index Patient ◽  
Becker Muscular Dystrophy ◽  
Large Size ◽  
Different Populations ◽  
The Mean ◽  
Deletion Frequency

Background: Duchenne muscular dystrophy (DMD), a lethal X-linked disease affecting 1 in 3500 male births, and its more benign variant, Becker muscular dystrophy (BMD), are caused by mutations in the dystrophin gene. Because of its large size, analysing the whole gene is impractical. Methods have been developed to detect the commonest mutations i.e. the deletions of the exons. Although these tests are highly specific, their sensitivity is inherently limited by the prevalence of deletions, which differs among different populations.Methods: We reviewed our database for the detection of Dystrophin gene mutation by means of 31-exon multiplex PCR in Thai males, diagnosed clinically and biochemically with DMD or BMD from July 1994 to November 2006. One index patient was chosen from each family for statistical analysis. The overall sensitivity of the test, the number of fragment deleted, and the deletion frequency of each fragment were calculated, along with their 95% confidence intervals (C.I.).Results: We found deletions in 99 out of the 202 index patients (49%; Bayesian 95% C.I. = 42%–56%). 51% of these had deletion in only one of the 31 exons tested, while the patient with the most extensive deletions had 14 exons deleted. The mean number of deleted exons were 2.84 (BCabootstrap 95% C.I. = 2.37–3.48), or 5.02 (3.81–6.85) if all the untested exons adjacent to the confirmed deleted exons were assumed to be deleted. The region spanning exons 44-52 was the most frequently deleted. These were similar to those reported in the Japanese.Conclusion: The multiplex PCR detected deletions only in about half of the Thai patients. The diseases therefore should not be excluded solely on the negative result if DMD/BMD is strongly suspected.

scholarly journals Unexpected DMD Gene Mutations Detected by CMA and CNV-seq in amniotic Fluid and Aborted Fetus Samples

2021 ◽  
Author(s):  
Qiuhua Wu ◽  
Lihui Yang ◽  
Qiujie Jin ◽  
Rui Wang ◽  
Wen Zhai ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Muscular Dystrophy ◽  
Amniotic Fluid ◽  
Spontaneous Abortion ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Hereditary Diseases ◽  
Muscle Dysfunction ◽  
Dmd Gene

Abstract Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X chromosome-linked recessive hereditary diseases. The mechanism is that the exon mutations of anti-myatrophy protein gene (Dystrophin gene) and lead to muscle dysfunction. Prenatal diagnosis can prevent the birth of children with defects and have good clinical significance. Methods: CMA and CNV-seq were used to detect the amniotic fluid after amniocentesis,. CNV-seq was used to detect spontaneous abortion tissue. The DMD gene mutations were found in 6 amniotic fluid samples and one spontaneous abortion sample. DMD gene mutations were confirmed by MLPA and new DMD mutations were found.Results: CMA found DMD mutations :1.Xp21.1, 75.5kb del (E52-53); 2.Xp21.2, 334.92kb dup (E61-79); 3.Xp21.2, 292.25kb dup (E58-74); 4.Xp21.1, 374.20 kb dup (E45-51). CNV-seq found DMD mutations: 5.X p21.2, E64-79 dup; 6.X p21.1, E1-7dup; 7.Xp21.1, E 44-52 del. Conclusions: 4 fetuses harboring DMD gene mutations were found by CMA, 2 fetuses and 1 induced abortion carrying DMD gene mutations was detected by CNV-seq. CMA/CNV-seq jointed with MLPA test can provide more comprehensive evidence for prenatal diagnosis.

scholarly journals Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

2019 ◽  
Vol 8 ◽  
pp. 204800401987958
Author(s):  
HR Spaulding ◽  
C Ballmann ◽  
JC Quindry ◽  
MB Hudson ◽  
JT Selsby
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Mdx Mice ◽  
Dystrophin Deficiency ◽  
Muscle Wasting Disease ◽  
Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

scholarly journals Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 554
Author(s):  
Nika V. Petrova ◽  
Nataliya Y. Kashirskaya ◽  
Tatyana A. Vasilyeva ◽  
Elena I. Kondratyeva ◽  
Elena K. Zhekaite ◽  
...  
Keyword(s):  
Ethnic Groups ◽  
Mutant Allele ◽  
Gene Mutations ◽  
Copy Number Variations ◽  
Comprehensive Analysis ◽  
Mutation Spectrum ◽  
Cftr Mutations ◽  
The Russian Federation ◽  
Numerous People ◽  
Dependent Probe

The distribution and frequency of the CFTR gene mutations vary considerably between countries and ethnic groups. Russians are an East Slavic ethnic groups are native to Eastern Europe. Russians, the most numerous people of the Russian Federation (RF), make about 80% of the population. The aim is to reveal the molecular causes of CF in ethnic Russian patients as comprehensively as possible. The analysis of most common CFTR mutations utilized for CF diagnosis in multiethnic RF population accounts for about 83% of all CF-causing mutations in 1384 ethnic Russian patients. Variants c.1521_1523delCTT (F508del), c.54-5940_273+10250del21kb (CFTRdele2,3), c.2012delT (2143delT), c.2052_2053insA (2184insA), and c.3691delT (3821delT) are most typical for CF patients of Russian origin. DNA of 154 CF patients, Russian by origin, in whom at least one mutant allele was not previously identified (164 CF alleles), was analyzed by Sanger sequencing followed by the multiplex ligase-dependent probe amplification (MLPA) method. In addition to the 29 variants identified during the previous test for common mutations, 91 pathogenic CFTR variants were also revealed: 29 missense, 19 nonsense, 14 frame shift in/del, 17 splicing, 1 in frame ins, and 11 copy number variations (CNV). Each of the 61 variants was revealed once, and 17 twice. Each of the variants c.1209G>C (E403D), c.2128A>T (K710X), c.3883delA (4015delA), and c.3884_3885insT (4016insT) were detected for three, c.1766+1G>A (1898+1G>A) and c.2834C>T (S945L) for four, c.1766+1G>C (1898+1G>C) and c.(743+1_744-1)_(1584+1_1585-1)dup (CFTRdup6b-10) for five, c.2353C>T (R785X) and c.4004T>C (L1335P) for six, c.3929G>A (W1310X) for seven, c.580-1G>T (712-1G>T for eight, and c.1240_1244delCAAAA (1365del5) for 11 unrelated patients. A comprehensive analysis of CFTR mutant alleles with sequencing followed by MLPA, allowed not only the identification of 163 of 164 unknown alleles in our patient sample, but also expansion of the mutation spectrum with novel and additional frequent variants for ethnic Russians.

scholarly journals Cardiac Involvement in Dystrophin-Deficient Females: Current Understanding and Implications for the Treatment of Dystrophinopathies

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 765 ◽  
Author(s):  
Kenji Rowel Q. Lim ◽  
Narin Sheri ◽  
Quynh Nguyen ◽  
Toshifumi Yokota
Keyword(s):  
Muscular Dystrophy ◽  
Molecular Mechanisms ◽  
Cardiac Involvement ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Female Carrier ◽  
Daily Life Activities ◽  
Cardiac Manifestations ◽  
Available Information

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive condition caused primarily by out-of-frame mutations in the dystrophin gene. In males, DMD presents with progressive body-wide muscle deterioration, culminating in death as a result of cardiac or respiratory failure. A milder form of DMD exists, called Becker muscular dystrophy (BMD), which is typically caused by in-frame dystrophin gene mutations. It should be emphasized that DMD and BMD are not exclusive to males, as some female dystrophin mutation carriers do present with similar symptoms, generally at reduced levels of severity. Cardiac involvement in particular is a pressing concern among manifesting females, as it may develop into serious heart failure or could predispose them to certain risks during pregnancy or daily life activities. It is known that about 8% of carriers present with dilated cardiomyopathy, though it may vary from 0% to 16.7%, depending on if the carrier is classified as having DMD or BMD. Understanding the genetic and molecular mechanisms underlying cardiac manifestations in dystrophin-deficient females is therefore of critical importance. In this article, we review available information from the literature on this subject, as well as discuss the implications of female carrier studies on the development of therapies aiming to increase dystrophin levels in the heart.

The First Reported Case of Prenatal Diagnosis for Pyruvate Kinase Deficiency in a Chinese Family

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5276-5276
Author(s):  
Jason CC So ◽  
Mary Tang ◽  
Rever Li ◽  
Shau Yin Ha ◽  
Serge Pissard ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Prenatal Diagnosis ◽  
Ethnic Groups ◽  
Pyruvate Kinase ◽  
Hemolytic Anemia ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Chinese Family ◽  
First Case

Abstract Abstract 5276 Pyruvate kinase (PK) deficiency of red cells (EC: 2.7.1.40) is the commonest inherited enzyme deficiency in the glycolytic pathway, leading to chronic non-spherocytic hemolytic anemia (CNSHA). There are over 220 characterized mutations deposited in a public database (PKLR Mutation Database http://www.pklrmutationdatabase.com). Heterozygous carriers are asymptomatic but homozygotes or compound heterozygotes can have significant anemia leading to transfusion dependency, neonatal death and hydrops fetalis. All ethnic groups are affected but data on Chinese are very scanty. We describe the first case of prenatal diagnosis for PK deficiency in Chinese and emphasize that this disease is an important differential diagnosis in pediatric patients with hemolytic anemia. A Han Chinese presented with hepatosplenomegaly, severe anemia and unconjugated hyperbilirubinemia at birth, necessitating exchange transfusion on day 1 and prolonged phototherapy till day 10 of life. Glucose-6-phosphate dehydrogenase level was normal. His parents were unrelated and asymptomatic. Family history was unremarkable. He developed severe CNSHA on follow up, requiring monthly red cell transfusion to relieve symptoms and to maintain satisfactory growth. Iron chelation therapy was started at 2 years of age and splenectomy was performed at 4 years to reduce transfusion requirement. The baseline PK enzyme level was not known but both parents had a mildly reduced PK level. Genetic analysis of PKLR gene was performed. All 11 exons and promoter were screened using polymerase chain reaction (PCR)-denaturing high performance liquid chromatography followed by PCR-sequencing. The father was found to carry a mutation in exon 8: PKLR: c.1073 G>A (p.Gly358Glu) while the sequencing result was normal in the mother. Quantitative multiplex PCR of short fluorescent fragments detected a rare large deletion removing exon 4 to exon 10 of the PKLR gene in the mother. Gap-PCR mapping confirmed that it to be a deletion previously found in a Vietnamese family (Costa C et al Haematologica 2005) and an Australian family (Fermo E et al Br J Haematol 2005). Both mutations have not been previously reported in Chinese. The proband was found to carry the paternal point mutation and the maternal deletion. Because of the severe clinical course of their first child, the couple requested prenatal biopsy was performed at 12 week of gestation. The fetus was found to be simple heterozygous for the paternal mutation. Pregnancy was allowed to continue and a healthy baby was born. A PK assay performed at the age of 9 months was normal. Mutation studies in a peripheral blood sample at 10 months of age confirmed the PKLR genotype. There was no evidence of hemolytic anemia after 3 years of follow up. Because of its perceived rarity and benignity in many ethnic groups, PK deficiency does not enter early into the differential diagnosis of anemia in pediatric patients. Its potential to cause severe disease is often overlooked and delay in diagnosis is common (Pissard S et al J Pediatr 2007). Genetic characterization and genotype-phenotype correlation studies on PKLR in different populations are indicated to better characterize the disease spectrum and to define the role of prenatal diagnosis in PK deficiency. Disclosures: No relevant conflicts of interest to declare.

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