Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients
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 cytoge...
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doaj-8b7cbd26a1754a4f8a98a8faef870caf2020-11-24T21:08:39ZengWolters Kluwer Medknow PublicationsIndian Journal of Medical Research0971-59162014-01-0113916675Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patientsVijay R BoggulaAnju ShuklaSumita DandaSankar V HariharanSheela NampoothiriRashmi KumarShubha R PhadkeBackground & 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 microdeletion/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.http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2014;volume=139;issue=1;spage=66;epage=75;aulast=BoggulaCommon microdeletion/microduplication syndromes - developmental delay - intellectual disability - India - MLPA - subtelomeric abnormalities |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Vijay R Boggula Anju Shukla Sumita Danda Sankar V Hariharan Sheela Nampoothiri Rashmi Kumar Shubha R Phadke |
spellingShingle |
Vijay R Boggula Anju Shukla Sumita Danda Sankar V Hariharan Sheela Nampoothiri Rashmi Kumar Shubha R Phadke Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients Indian Journal of Medical Research Common microdeletion/microduplication syndromes - developmental delay - intellectual disability - India - MLPA - subtelomeric abnormalities |
author_facet |
Vijay R Boggula Anju Shukla Sumita Danda Sankar V Hariharan Sheela Nampoothiri Rashmi Kumar Shubha R Phadke |
author_sort |
Vijay R Boggula |
title |
Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients |
title_short |
Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients |
title_full |
Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients |
title_fullStr |
Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients |
title_full_unstemmed |
Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients |
title_sort |
clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: a study in 203 indian patients |
publisher |
Wolters Kluwer Medknow Publications |
series |
Indian Journal of Medical Research |
issn |
0971-5916 |
publishDate |
2014-01-01 |
description |
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 microdeletion/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. |
topic |
Common microdeletion/microduplication syndromes - developmental delay - intellectual disability - India - MLPA - subtelomeric abnormalities |
url |
http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2014;volume=139;issue=1;spage=66;epage=75;aulast=Boggula |
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