High rate of detection of subtelomeric aberration by using combined MLPA and subtelomeric FISH approach in patients with moderate to severe mental retardation.

OBJECTIVES: (1) To evaluate the prevalence of subtelomeric deletion in moderate to severe mental retardation population, (2) to assess the feasibility and cost-effectiveness of combined methodology in routine workup of this sub-population. METHOD: Twenty unrelated patients using strict selection criteria were recruited for the study from the Clinical Genetic Service. Patients were initially screened by Multiplex Ligation-dependent Probe Amplification (MLPA) for subtelomeric imbalance followed by FISH analysis for anatomical integrity. This is then followed by parental subtelomeric FISH analysis. RESULTS: Three subtelomeric deletions were identified. They were Deletion 1p36, Deletion 1q44 and Deletion 10q26; these were previously unidentified by conventional technique. CONCLUSIONS: The prevalence of subtelomeric deletion in our cohort of moderate to severe mental retardation patients is consistent with published findings of around 10%. The figure is on the higher side if more stringent criteria is used. The combination of strict clinical criteria, MLPA and selective subtelomeric FISH was shown to be feasible and cost-effective.

Detecting exon deletions and duplications of the DMD gene using Multiplex Ligation-dependent Probe Amplification (MLPA).

OBJECTIVES: To evaluate the efficacy of Multiplex Ligation-dependent Probe Amplification (MLPA) technique in comparison with the traditional multiplex PCR assay in detection of exon deletions and duplications of the DMD gene. DESIGN AND METHODS: The sensitivity and accuracy of MLPA were assessed and compared with the multiplex PCR in a total of 63 subjects including 43 subjects with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) and 20 female carriers. RESULTS: MLPA was able to detect all the known deletions and duplications; it detected four additional mutations that had been missed by multiplex PCR. In addition, the extent of the deletions and duplications could be more accurately defined which in turn facilitated a genotype-phenotype correlation. CONCLUSIONS: MLPA is superior to multiplex PCR. It should be the method of choice for the detection of exon deletions and duplications of the DMD gene in patients with DMD or BMD, as well as in female carriers.