Screening for subtelomeric rearrangements in 210 patients with unexplained mental retardation using multiplex ligation dependent probe amplification (MLPA)

Koolen, David A.; Nillesen, Willy M.; Versteeg, Marlies; Merkx, G.F.M.; Knoers, Nine V A M; Kets, Marleen; Vermeer, Sascha; Ravenswaaij, Conny M. A. van; Kovel, Carolien G.F. de; Brunner, Han G.; Smeets, Dominique; Vries, Bert B.A. de; Sistermans, Erik A.

doi:10.1136/jmg.2004.023671

Cited by 144 publications

(145 citation statements)

References 24 publications

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“…Furthermore, a home-designed kit was used containing synthetic probes including all coding exons (also exon 6). The analysis and data processing were performed as described by Koolen et al 17 …”

Section: Multiplex Ligand-dependent Probe Amplificationmentioning

confidence: 99%

Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome

et al. 2011

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Gitelman syndrome (GS) is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis in conjunction with significant hypomagnesemia and hypocalciuria. The GS phenotype is caused by mutations in the solute carrier family 12, member 3 (SLC12A3) gene that encodes the thiazide-sensitive NaCl cotransporter (NCC). We analyzed DNA samples of 163 patients with a clinical suspicion of GS by direct sequencing of all 26 exons of the SLC12A3 gene. In total, 114 different mutations were identified, 31 of which have not been reported before. These novel variants include 3 deletions, 18 missense, 6 splice site and 4 nonsense mutations. We selected seven missense mutations to investigate their effect on NCC activity and plasma membrane localization by using the Xenopus laevis oocyte expression system. The Thr392Ile mutant did not display transport activity (probably class 2 mutation), while the Asn442Ser and Gln1030Arg NCC mutants showed decreased plasma membrane localization and consequently function, likely due to impaired trafficking (class 3 mutation). Even though the NaCl uptake was hampered for NCC mutants Glu121Asp, Pro751Leu, Ser475Cys and Tyr489His, the transporters reached the plasma membrane (class 4 mutation), suggesting an effect on NCC regulation or ion affinity. The present study shows the identification of 38 novel mutations in the SLC12A3 gene and provides insight into the mechanisms that regulate NCC.

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Section: Multiplex Ligand-dependent Probe Amplificationmentioning

confidence: 99%

Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome

et al. 2011

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“…2b). 9,10 The synthetic MLPA probes were created in accordance with the protocol provided by MRC-Holland (http://www.mlpa.com). Furthermore, the deletion of the specific SLC2A1 (GLUT1) gene was confirmed by MLPA with probes hybridizing to the 10 different exons within the gene (SALSA MLPA-kit P138 [MRC-Holland, Amerstam, the Netherlands]).…”

Section: Array-based Comparative Genomic Hybridizationmentioning

confidence: 99%

A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development

Vermeer

Koolen

Visser

et al. 2007

Develop Med Child Neuro

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A de novo 4.1‐megabase microdeletion of chromosome 1p34.2p34.3 has been identified by array‐based comparative genomic hybridization in a young male with severely delayed development, microcephaly, pronounced hypotonia, and facial dysmorphism. The deleted region encompasses 48 genes, among them the glucose transporter 1 (SLC2A1 or GLUT1) gene. The deletion of the GLUT1 gene was in line with the abnormal ratio of cerebrospinal fluid (CSF) glucose to blood glucose, indicative of GLUT1 deficiency syndrome (MIM #606777). GLUT1 deficiency syndrome is characterized by therapy‐resistant infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and a low concentration of glucose in the CSF. It is known that a ketogenic diet can lead to better control of seizures. This case study shows that identifying a microdeletion as the cause of learning disability is not only important for genetic counselling but might also lead to therapeutic intervention.

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“…Synthetic 5¢ or 3¢ halfprobes were obtained from Biolegio (Malden, The Netherlands). Hybridisation, ligation and amplification of the MLPA probes were performed as described previously (Koolen et al 2004;Schouten et al 2002). Amplification products were identified and quantified by capillary electrophoresis on an ABI 3730 genetic analyzer, using GeneMapper software (Applied Biosystems, Foster City, CA).…”

Section: Array Cgh and Confirmationmentioning

confidence: 99%

“…Amplification products were identified and quantified by capillary electrophoresis on an ABI 3730 genetic analyzer, using GeneMapper software (Applied Biosystems, Foster City, CA). Data were normalised as described by Koolen et al (2004).…”

Section: Array Cgh and Confirmationmentioning

confidence: 99%

Holoprosencephaly and preaxial polydactyly associated with a 1.24 Mb duplication encompassing FBXW11 at 5q35.1

et al. 2006

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Screening for subtelomeric rearrangements in 210 patients with unexplained mental retardation using multiplex ligation dependent probe amplification (MLPA)

Cited by 144 publications

References 24 publications

Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome

Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome

A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development

Holoprosencephaly and preaxial polydactyly associated with a 1.24 Mb duplication encompassing FBXW11 at 5q35.1

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