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

Abstract

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 (BCa bootstrap 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.

Gene Frequencies of the Human GSTT1 (Null Allele) and GSTP1 (Ile105Val) Polymorphisms among South Indian Populations

“…The prevalence of GSTT1 null allele in the present study ranges from 11% to 22%, which is almost similar to the frequencies reported in Caucasians (Blackburn et al, 2006;Johansson et al, 1998;Mannervik et al, 2005). Korean population showed higher frequency of (45.3%) of GSTT1 null allele compared with the white Americans (20.4%), African Americans (21.8%), Mexican-Americans (9.7%) (Hoglund et al, 2009;Marinkovic et al, 2008) and Turkish populations (10.8-28.3%) (Oke et al, 1998;Shchipanov et al, 2008;Sura et al, 2008). The GSTT1 null allele frequency in Native Russians is very close to allelic frequencies observed in some European populations (Baysal et al, 2008).…”

Distribution of dystrophin gene deletions in a Chinese population

“…Reported deletion detection rates vary widely, ranging between 31% and 73.86%. 11 – 24 These differences may be caused by many factors such as race, sample size and inclusion criteria. It has been suggested that the relatively low deletion detection rate in some studies is caused by the inclusion of other similar muscle diseases, because diagnosis was based mainly on clinical symptoms and did not require muscle biopsy.…”

“…It has been suggested that the relatively low deletion detection rate in some studies is caused by the inclusion of other similar muscle diseases, because diagnosis was based mainly on clinical symptoms and did not require muscle biopsy. 17 , 21 Further, detailed studies are needed to verify the relationship between deletion frequency and population.…”

Novel mutation in exon 56 of the dystrophin gene in a child with Duchenne muscular dystrophy

“…Muscular dystrophy (MD) refers to a genetically heterogeneous group of degenerative muscle disorders that are characterized by the progressive loss of muscle strength and integrity (1), and the most common and severe type of MD is Duchenne muscular dystrophy (DMD; MIM#310200), which accounts for more than half of all MD cases (2-4) and affects approximately 1 in 3,500 live male newborns (5,6). This disease is associated with continuous cycles of muscle cell regeneration and degeneration, ultimately resulting in the failure of muscle regeneration; the muscle is substituted by fat and connective tissue.…”