Prenatal Diagnosis of Dystrophin Gene Mutations using Multiplex Ligation Dependent Probe Amplification (MLPA) for Duchene Muscular Dystrophy
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2019, Vol 12, Issue 3
Abstract
Duchene muscular dystrophy (DMD) is a common X-chromosomal recessive disorders caused by mutations in the dystrophin gene. Male children are primarily affected by the disease, characterized by progressive muscular wasting. The worldwide incidence of DMD is estimated at 1 in 3500 - 5000 male births. At present, there is no effective treatment for DMD, and there is a need for early diagnosis and pre-natal testing for dystrophin gene mutations. We describe the use of Multiple Probe Ligation and Amplification assay (MLPA) for diagnosis of dystrophin gene mutations in an amniocentesis sample tested at 16 weeks of gestation. The patient had a family history of DMD and also a child with DMD. In this case the sample was identified to be of a female fetus with a heterozygous deletion in dystrophin exons 49-50. Pre-natal diagnosis of DMD is an effective way for early identification of high risk cases suspected for DMD.Duchene muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X-chromosomal recessive disorders caused by mutations in the dystrophin gene. Male children are primarily affected by the disease, which is characterized by progressive muscular wasting and increased serum creatine kinase. The worldwide incidence of DMD is estimated to be about 1 in 3, 500 to 1 in 5,000 male births [1]. In Pakistan, the incidence has not been reported, however few isolated studies have reported the gene mutation analysis patterns in the both distal and proximal hot spots in the effected patients [2-3]. DMD and BMD genotypes are characterized by mutations in the dystrophin gene, which has 79 exons. Up to 70% of DMD are associated with deletions, and 5-10% with duplications in the gene. However, approximately 25% to 30% of boys with DMD, and 5% to 10% of boys with BMD do not have whole exon deletions or duplications but have other small insertions/deletions/point mutations. Genetic conditions are broadly classified into those which are either dominant or recessive and may be associated with either autosomes or sex-chromosomes. If the disease is X-linked, then a male individual with an X and Y chromosome with a mutation on the X chromosome would necessarily be affected by the disease condition. However, a female individual with the mutation may not be affected to the same extent as they would have a normal X-chromosome to compensate for the mutation present. However, such a female individual who is heterozygous for the disease causing mutation may be termed as a ‘carrier’ for the disease [4]. As DMD is an X-linked disease, mothers with dystrophin gene mutations may be carriers who transfer risk for DMD to their off-spring [5-6]. Following that, female offspring may themselves be affected carriers while male offspring would definitely have DMD. Pre-natal testing performed during pregnancy can determine the genotype of the fetus. This allows the parents to make an informed decision to be prepared for a child with a likelihood for disease armed with knowledge that will help them to prepare and plan for the future or, to make a decision regarding the pregnancy outcome.
Authors and Affiliations
Asghar Nasir, Zeeshan Ansar, Shama Munim, Kahkashan Imam, Zahra Hasan
Keywords
Related Articles
- EP ID EP592742
- DOI 10.26717/BJSTR.2018.12.002251
- Views 170
- Downloads 0
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