Comparative study of three diagnostic approaches (FISH, STRs and MLPA) in 30 patients with 22q11.2 deletion syndrome

Fernández, Luís; Lapunzina, Pablo; Arjona, Dolores; Pajares, I. López; Garcı́a-Guereta, Luis; Elorza, Dolores; Burgueros, Margarita; Torres, M. L. de; Mori, María Ángeles; Palomares, María; García‐Alix, Alfredo; Delicado, Alicia

doi:10.1111/j.1399-0004.2005.00493.x

Cited by 86 publications

(68 citation statements)

References 20 publications

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“…Other techniques (such as multiplex ligation-dependent probe amplification and BACs-on-Beads) have also been developed. 25,26 These techniques enable the diagnosis of 22q11.2DS in patients with atypical phenotypes and/or who have been missed by conventional cytogenetic techniques.…”

Section: Introductionmentioning

confidence: 99%

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Poirsier¹,

Besseau-Ayasse²,

Schluth-Bolard³

et al. 2015

Eur J Hum Genet

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Although 22q11.2 deletion syndrome (22q11.2DS) is the most recurrent human microdeletion syndrome associated with a highly variable phenotype, little is known about the condition's true incidence and the phenotype at diagnosis. We performed a multicenter, retrospective analysis of postnatally diagnosed patients recruited by members of the Association des Cytogénéticiens de Langue Française (the French-Speaking Cytogeneticists Association). Clinical and cytogenetic data on 749 cases diagnosed between 1995 and 2013 were collected by 31 French cytogenetics laboratories. The most frequent reasons for referral of postnatally diagnosed cases were a congenital heart defect (CHD, 48.6%), facial dysmorphism (49.7%) and developmental delay (40.7%). Since 2007 (the year in which array comparative genomic hybridization (aCGH) was introduced for the routine screening of patients with intellectual disability), almost all cases have been diagnosed using FISH (96.1%). Only 15 cases (all with an atypical phenotype) were diagnosed with aCGH; the deletion size ranged from 745 to 2904 kb. The deletion was inherited in 15.0% of cases and was of maternal origin in 85.5% of the latter. This is the largest yet documented cohort of patients with 22q11.2DS (the most commonly diagnosed microdeletion) from the same population. French cytogenetics laboratories diagnosed at least 108 affected patients (including fetuses) per year from among a national population of ∼ 66 million. As observed for prenatal diagnoses, CHDs were the most frequently detected malformation in postnatal diagnoses. The most common CHD in postnatal diagnoses was an isolated septal defect.

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Section: Introductionmentioning

confidence: 99%

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Poirsier¹,

Besseau-Ayasse²,

Schluth-Bolard³

et al. 2015

Eur J Hum Genet

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“…As stated by others, 7,8 MLPA has many advantages, as compared with standard FISH analysis: It is rapid, highly cost beneficial, and has a high resolution. FISH analysis is often based on commercially available probing for TUPLE1 or N25 situated in the proximal part of the typically deleted region.…”

Section: Discussionmentioning

confidence: 98%

“…5,6 Since 2002 it has been possible to detect copy number variations by multiplex ligation-dependent probe amplification (MLPA), and this method has been shown to be superior to fluorescence in situ hybridization (FISH). 7,8 The clinical diagnostic consequence of this was demonstrated by Stachon et al 9 who retested a group of 62 patients suspected of 22q11 DS. MLPA confirmed 22q11.2 deletions among 51 patients with positive FISH tests, and detected 2 deletions among the 11 patients with FISH negative results.…”

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confidence: 96%

Detecting 22q11.2 Deletions by Use of Multiplex Ligation-Dependent Probe Amplification on DNA from Neonatal Dried Blood Spot Samples

Sørensen

Agergaard

Olesen

et al. 2010

The Journal of Molecular Diagnostics

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The 22q11 deletion syndrome , which is caused by a 1.5-to 3.0-megabase hemizygous deletion in chromosome 22q11.2 , has a prevalence of 1/2000 to 1/4000. However , the syndrome presents with highly variable phenotypes and thus may be underestimated among Danish newborns. To establish a true incidence of 22q11.2 deletions among certain manifestations, eg, congenital heart disease , on selected Danes , a multiplex ligation-dependant probe amplification (MLPA) analysis was designed. The analysis was planned to be performed on DNA extracted from dried blood spot samples (DBSS) obtained from Guthrie cards collected during neonatal screening programs. However, the DNA concentration necessary for a standard MLPA analysis (20 ng) could not be attained from DBSS, and a novel MLPA design was developed to permit for analysis on limited amounts of DNA (2 ng). A pilot study is reported here that validates the new MLPA design using nine patients diagnosed with the 22q11.2 deletion and 101 controls. All deletions were identified using DNA extracted from DBSS , and no copy number variations were detected in the controls , resulting in a specificity and sensitivity of 100%. It is thereby concluded that the novel MLPA probe design is successful and reliable using minimal amounts of DNA. This allows for use of DBSS samples in a retrospective study of 22q11.2 deletion among certain manifestations associated with

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“…They appear predominantly in the subtelomeric regions, which include repetitive sequences and are therefore more susceptible to chromosomal rearrangements. Previous studies have shown that CNVs associated with intellectual disability (ID) and CA are significantly enriched in genes whose mouse orthologous produce a nervous system phenotype when disrupted [Ballif et al, 2007;De Vries et al, 2003;Fernandez et al, 2005;Leonard and Wen, 2002;Ravnan et al, 2006;Schouten et al, 2002;Shaffer et al, 2005;Shao et al, 2008]. …”

mentioning

confidence: 99%

“…Although chromosomal analysis is a standard procedure in patients with unexplained diagnosis (including DD/ID and multiple CA), evaluating these alterations using MLPA strategy enables one to assess all the subtelomeres at a relatively low cost and in a rapid single reaction [Schouten et al, 2002;Fernandez et al, 2005;Vorstman et al, 2006].…”

mentioning

confidence: 99%

Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in Patients with Congenital Anomalies and Developmental Disability

Novo-Filho

Montenegro²,

Zanardo³

et al. 2016

Cytogenet Genome Res

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The most prevalent structural variations in the human genome are copy number variations (CNVs), which appear predominantly in the subtelomeric regions. Variable sizes of 4p/4q CNVs have been associated with several different psychiatric findings and developmental disability (DD). We analyzed 105 patients with congenital anomalies (CA) and developmental and/or intellectual disabilities (DD/ID) using MLPA subtelomeric specific kits (P036 /P070) and 4 of them using microarrays. We found abnormal subtelomeric CNVs in 15 patients (14.3%), including 8 patients with subtelomeric deletions at 4p/4q (53.3%). Additional genomic changes were observed at 1p36, 2q37.3, 5p15.3, 5q35.3, 8p23.3, 13q11, 14q32.3, 15q11.2, and Xq28/Yq12. This indicates the prevalence of independent deletions at 4p/4q, involving PIGG, TRIML2, and FRG1. Furthermore, we identified 15 genes with changes in copy number that contribute to neurological development and/or function, among them CRMP1, SORCS2, SLC25A4, and HELT. Our results highlight the association of genes with changes in copy number at 4p and 4q subtelomeric regions and the DD phenotype. Cytogenomic characterization of additional cases with distal deletions should help clarifying the role of subtelomeric CNVs in neurological diseases.

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Comparative study of three diagnostic approaches (FISH, STRs and MLPA) in 30 patients with 22q11.2 deletion syndrome

Cited by 86 publications

References 20 publications

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Detecting 22q11.2 Deletions by Use of Multiplex Ligation-Dependent Probe Amplification on DNA from Neonatal Dried Blood Spot Samples

Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in Patients with Congenital Anomalies and Developmental Disability

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