title: Integrated multiplex ligation dependent probe amplification (MLPA) assays for the detection of alterations in the HEXB, GM2A and SMARCAL1 genes to support the diagnosis of Morbus Sandhoff, M. Tay-Sachs variant AB and Schimke immuno-osseous dysplasia in humans.
abstract: Multiplex ligation dependent probe amplification (MLPA) assays were designed for the genes HEXB (OMIM: 606873), GM2A (OMIM: 613109) and SMARCAL1 (OMIM: 606622) of humans. Two sets of synthetic MLPA probes for these coding exons were tested. Changes in copy numbers were detected as well as single nucleotide polymorphisms (SNPs) by complementary DNA sequence analyses. The MLPA method was shown to be reliable for mutation detection and identified five published and 12 new mutations. In all cases from a Morbus Sandhoff cohort of patients, exclusively one variation in copy number was observed and linked to a nucleotide alteration called c.1614-14C>A. This deletion comprised exons 1-5. One of these cases is described in detail. Deletions were neither detected in the GM2A nor the SMARCAL1 genes. The MLPA assays complement routine diagnostics for M. Sandhoff (OMIM: 268800), M. Tay-Sachs variant AB (OMIM: 272750) and Schimke immuno-osseous dysplasia (OMIM: 242900).
authors.affiliation: Human Genetics, Ruhr University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany.
authors.forename: Anna K U
authors.initials: AK
authors.lastname: Sobek
authors.forename: Christina
authors.initials: C
authors.lastname: Evers
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dekomien
mesh_terms: D001161:Arteriosclerosis / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D056915:DNA Copy Number Variations; D004265:DNA Helicases / Q000235:genetics; D049289:G(M2) Activator Protein / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000081207:Primary Immunodeficiency Diseases; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000235:genetics*; D012497:Sandhoff Disease / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D049290:Tay-Sachs Disease, AB Variant / Q000175:diagnosis / Q000235:genetics*; D054821:beta-Hexosaminidase beta Chain / Q000235:genetics
chemical_list: D049289:G(M2) Activator Protein; C412482:SMARCAL1 protein, human; C513386:HEXB protein, human; D054821:beta-Hexosaminidase beta Chain; D004265:DNA Helicases