Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation

A study in 203 indian patients

Vijay R. Boggula, Anju Shukla, Sumita Danda, Sankar V. Hariharan, Sheela Nampoothiri, Rashmi Kumar, Shubha R. Phadke

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background & objectives: Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many icrodeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. Methods: A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fluorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. Results: The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Interpretation & conclusions: Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalIndian Journal of Medical Research
Volume139
Publication statusPublished - 01-2014

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Multiplex Polymerase Chain Reaction
Intellectual Disability
Amplification
varespladib methyl
Cytogenetics
Smith-Magenis Syndrome
Williams Syndrome
DiGeorge Syndrome
Microarrays
Cytogenetic Analysis
X Chromosome
Fluorescence In Situ Hybridization
Genome
Costs and Cost Analysis
Chromosomes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Boggula, Vijay R. ; Shukla, Anju ; Danda, Sumita ; Hariharan, Sankar V. ; Nampoothiri, Sheela ; Kumar, Rashmi ; Phadke, Shubha R. / Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation : A study in 203 indian patients. In: Indian Journal of Medical Research. 2014 ; Vol. 139. pp. 66-75.
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Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation : A study in 203 indian patients. / Boggula, Vijay R.; Shukla, Anju; Danda, Sumita; Hariharan, Sankar V.; Nampoothiri, Sheela; Kumar, Rashmi; Phadke, Shubha R.

In: Indian Journal of Medical Research, Vol. 139, 01.2014, p. 66-75.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation

T2 - A study in 203 indian patients

AU - Boggula, Vijay R.

AU - Shukla, Anju

AU - Danda, Sumita

AU - Hariharan, Sankar V.

AU - Nampoothiri, Sheela

AU - Kumar, Rashmi

AU - Phadke, Shubha R.

PY - 2014/1

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AB - Background & objectives: Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many icrodeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. Methods: A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fluorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. Results: The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Interpretation & conclusions: Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID.

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