Datasets:

ncbi_disease

like 38

[ "Risk", "reversals", "in", "predictive", "testing", "for", "Huntington", "disease", "." ]

[ 0, 0, 0, 0, 0, 0, 1, 2, 0 ]

[ "The", "first", "predictive", "testing", "for", "Huntington", "disease", "(", "HD", ")", "was", "based", "on", "analysis", "of", "linked", "polymorphic", "DNA", "markers", "to", "estimate", "the", "likelihood", "of", "inheriting", "the", "mutation", "for", "HD", "." ]

[ 0, 0, 0, 0, 0, 1, 2, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0 ]

[ "Limits", "to", "accuracy", "included", "recombination", "between", "the", "DNA", "markers", "and", "the", "mutation", ",", "pedigree", "structure", ",", "and", "whether", "DNA", "samples", "were", "available", "from", "family", "members", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "With", "direct", "tests", "for", "the", "HD", "mutation", ",", "we", "have", "assessed", "the", "accuracy", "of", "results", "obtained", "by", "linkage", "approaches", "when", "requested", "to", "do", "so", "by", "the", "test", "individuals", "." ]

[ 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "For", "six", "such", "individuals", ",", "there", "was", "significant", "disparity", "between", "the", "tests", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Three", "went", "from", "a", "decreased", "risk", "to", "an", "increased", "risk", ",", "while", "in", "another", "three", "the", "risk", "was", "decreased", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Knowledge", "of", "the", "potential", "reasons", "for", "these", "changes", "in", "results", "and", "impact", "of", "these", "risk", "reversals", "on", "both", "patients", "and", "the", "counseling", "team", "can", "assist", "in", "the", "development", "of", "strategies", "for", "the", "prevention", "and", ",", "where", "necessary", ",", "management", "of", "a", "risk", "reversal", "in", "any", "predictive", "testing", "program", ".", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "A", "novel", "common", "missense", "mutation", "G301C", "in", "the", "N", "-", "acetylgalactosamine", "-", "6", "-", "sulfate", "sulfatase", "gene", "in", "mucopolysaccharidosis", "IVA", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0 ]

[ "Mucopolysaccharidosis", "IVA", "(", "MPS", "IVA", ")", "is", "an", "autosomal", "recessive", "lysosomal", "storage", "disorder", "caused", "by", "a", "genetic", "defect", "in", "N", "-", "acetylgalactosamine", "-", "6", "-", "sulfate", "sulfatase", "(", "GALNS", ")", "." ]

[ 1, 2, 0, 1, 2, 0, 0, 0, 1, 2, 2, 2, 2, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "previous", "studies", ",", "we", "have", "found", "two", "common", "mutations", "in", "Caucasians", "and", "Japanese", ",", "respectively", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "To", "characterize", "the", "mutational", "spectrum", "in", "various", "ethnic", "groups", ",", "mutations", "in", "the", "GALNS", "gene", "in", "Colombian", "MPS", "IVA", "patients", "were", "investigated", ",", "and", "genetic", "backgrounds", "were", "extensively", "analyzed", "to", "identify", "racial", "origin", ",", "based", "on", "mitochondrial", "DNA", "(", "mtDNA", ")", "lineages", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Three", "novel", "missense", "mutations", "never", "identified", "previously", "in", "other", "populations", "and", "found", "in", "16", "out", "of", "19", "Colombian", "MPS", "IVA", "unrelated", "alleles", "account", "for", "84", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0 ]

[ "2", "%", "of", "the", "alleles", "in", "this", "study", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "G301C", "and", "S162F", "mutations", "account", "for", "68", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "4", "%", "and", "10", "." ]

[ 0, 0, 0, 0, 0 ]

[ "5", "%", "of", "mutations", ",", "respectively", ",", "whereas", "the", "remaining", "F69V", "is", "limited", "to", "a", "single", "allele", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "skewed", "prevalence", "of", "G301C", "in", "only", "Colombian", "patients", "and", "haplotype", "analysis", "by", "restriction", "fragment", "length", "polymorphisms", "in", "the", "GALNS", "gene", "suggest", "that", "G301C", "originated", "from", "a", "common", "ancestor", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Investigation", "of", "the", "genetic", "background", "by", "means", "of", "mtDNA", "lineages", "indicate", "that", "all", "our", "patients", "are", "probably", "of", "native", "American", "descent" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Low", "frequency", "of", "BRCA1", "germline", "mutations", "in", "45", "German", "breast", "/", "ovarian", "cancer", "families", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0 ]

[ "In", "this", "study", "we", "investigated", "45", "German", "breast", "/", "ovarian", "cancer", "families", "for", "germline", "mutations", "in", "the", "BRCA1", "gene", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "We", "identified", "four", "germline", "mutations", "in", "three", "breast", "cancer", "families", "and", "in", "one", "breast", "-", "ovarian", "cancer", "family", ".", "among", "these", "were", "one", "frameshift", "mutation", ",", "one", "nonsense", "mutation", ",", "one", "novel", "splice", "site", "mutation", ",", "and", "one", "missense", "mutation", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "missense", "mutation", "was", "also", "found", "in", "2", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "8", "%", "of", "the", "general", "population", ",", "suggesting", "that", "it", "is", "not", "disease", "associated", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "average", "age", "of", "disease", "onset", "in", "those", "families", "harbouring", "causative", "mutations", "was", "between", "32", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "3", "and", "37", "." ]

[ 0, 0, 0, 0 ]

[ "4", "years", ",", "whereas", "the", "family", "harbouring", "the", "missense", "mutation", "had", "an", "average", "age", "of", "onset", "of", "51", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "2", "years", "." ]

[ 0, 0, 0 ]

[ "These", "findings", "show", "that", "BRCA1", "is", "implicated", "in", "a", "small", "fraction", "of", "breast", "/", "ovarian", "cancer", "families", "suggesting", "the", "involvement", "of", "another", "susceptibility", "gene", "(", "s", ")" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Paternal", "transmission", "of", "congenital", "myotonic", "dystrophy", "." ]

[ 0, 0, 0, 1, 2, 2, 0 ]

[ "We", "report", "a", "rare", "case", "of", "paternally", "transmitted", "congenital", "myotonic", "dystrophy", "(", "DM", ")", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 1, 0, 0 ]

[ "The", "proband", "is", "a", "23", "year", "old", ",", "mentally", "retarded", "male", "who", "suffers", "severe", "muscular", "weakness", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 1, 2, 0 ]

[ "He", "presented", "with", "respiratory", "and", "feeding", "difficulties", "at", "birth", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "His", "two", "sibs", "suffer", "from", "childhood", "onset", "DM", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 1, 0 ]

[ "Their", "late", "father", "had", "the", "adult", "type", "of", "DM", ",", "with", "onset", "around", "30", "years", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0 ]

[ "Only", "six", "other", "cases", "of", "paternal", "transmission", "of", "congenital", "DM", "have", "been", "reported", "recently", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0 ]

[ "We", "review", "the", "sex", "related", "effects", "on", "transmission", "of", "congenital", "DM", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0 ]

[ "Decreased", "fertility", "of", "males", "with", "adult", "onset", "DM", "and", "contraction", "of", "the", "repeat", "upon", "male", "transmission", "contribute", "to", "the", "almost", "absent", "occurrence", "of", "paternal", "transmission", "of", "congenital", "DM", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0 ]

[ "Also", "the", "fathers", "of", "the", "reported", "congenitally", "affected", "children", "showed", ",", "on", "average", ",", "shorter", "CTG", "repeat", "lengths", "and", "hence", "less", "severe", "clinical", "symptoms", "than", "the", "mothers", "of", "children", "with", "congenital", "DM", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0 ]

[ "We", "conclude", "that", "paternal", "transmission", "of", "congenital", "DM", "is", "rare", "and", "preferentially", "occurs", "with", "onset", "of", "DM", "past", "30", "years", "in", "the", "father", ".", "." ]

[ 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "RB1", "gene", "mutation", "in", "a", "child", "with", "ectopic", "intracranial", "retinoblastoma", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0 ]

[ "The", "RB1", "gene", "mutation", "was", "investigated", "in", "a", "child", "with", "ectopic", "intracranial", "retinoblastoma", "using", "DNA", "obtained", "from", "both", "the", "pineal", "and", "retinal", "tumours", "of", "the", "patient", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0, 0, 0 ]

[ "A", "nonsense", "mutation", "in", "exon", "17", "(", "codon", "556", ")", "of", "the", "RB1", "gene", "was", "found", "to", "be", "present", "homozygously", "in", "both", "the", "retinal", "and", "the", "pineal", "tumours", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 2, 0 ]

[ "The", "same", "mutation", "was", "present", "heterozygously", "in", "the", "DNA", "from", "the", "constitutional", "cells", "of", "the", "patient", ",", "proving", "it", "to", "be", "of", "germline", "origin", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "initial", "mutation", "was", "shown", "to", "have", "occurred", "in", "the", "paternally", "derived", "RB1", "allele", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "mutation", "is", "in", "an", "area", "of", "the", "gene", "that", "encodes", "the", "protein", "-", "binding", "region", "known", "as", "the", "pocket", "region", "and", "has", "been", "detected", "in", "other", "cases", "of", "retinoblastoma", ".", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0 ]

[ "Low", "levels", "of", "beta", "hexosaminidase", "A", "in", "healthy", "individuals", "with", "apparent", "deficiency", "of", "this", "enzyme", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Appreciable", "beta", "hexosaminidase", "A", "(", "hex", "A", ")", "activity", "has", "been", "detected", "in", "cultured", "skin", "fibroblasts", "and", "melanoma", "tissue", "from", "healthy", "individuals", "previously", "reported", "as", "having", "deficiency", "of", "hex", "A", "activity", "indistinguishable", "from", "that", "of", "patients", "with", "Tay", "-", "Sachs", "disease", "(", "TSD", ")", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0, 1, 0, 0 ]

[ "Identification", "and", "quantitation", "of", "hex", "A", ",", "amounting", "to", "3", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "5", "%", "-", "6", "." ]

[ 0, 0, 0, 0, 0 ]

[ "9", "%", "of", "total", "beta", "hexosaminidase", "activity", ",", "has", "been", "obtained", "by", "cellulose", "acetate", "gel", "electrophoresis", ",", "DEAE", "-", "cellulose", "ion", "-", "exchange", "chromatography", ",", "radial", "immunodiffusion", ",", "and", "radioimmunoassay", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Previous", "family", "studies", "suggested", "that", "these", "individuals", "may", "be", "compound", "heterozygotes", "for", "the", "common", "mutant", "TSD", "gene", "and", "a", "rare", "(", "allelic", ")", "mutant", "gene", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Thus", ",", "the", "postulated", "rate", "mutant", "gene", "appears", "to", "code", "for", "the", "expression", "of", "low", "amounts", "of", "hex", "A", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Heterozygotes", "for", "the", "rare", "mutant", "may", "be", "indistinguishable", "from", "heterozygotes", "for", "the", "common", "TSD", "mutant", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0 ]

[ "However", ",", "direct", "visualization", "and", "quantitation", "of", "hex", "A", "by", "the", "methods", "described", "may", "prevent", "false", "-", "positive", "prenatal", "diagnosis", "of", "TSD", "in", "fetuses", "having", "the", "incomplete", "hex", "A", "deficiency", "of", "the", "type", "described", "in", "the", "four", "healthy", "individuals" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "tumor", "suppressor", "gene", "Smad4", "/", "Dpc4", "is", "required", "for", "gastrulation", "and", "later", "for", "anterior", "development", "of", "the", "mouse", "embryo", "." ]

[ 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Mutations", "in", "the", "SMAD4", "/", "DPC4", "tumor", "suppressor", "gene", ",", "a", "key", "signal", "transducer", "in", "most", "TGFbeta", "-", "related", "pathways", ",", "are", "involved", "in", "50", "%", "of", "pancreatic", "cancers", "." ]

[ 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0 ]

[ "Homozygous", "Smad4", "mutant", "mice", "die", "before", "day", "7", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "5", "of", "embryogenesis", "." ]

[ 0, 0, 0, 0 ]

[ "Mutant", "embryos", "have", "reduced", "size", ",", "fail", "to", "gastrulate", "or", "express", "a", "mesodermal", "marker", ",", "and", "show", "abnormal", "visceral", "endoderm", "development", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Growth", "retardation", "of", "the", "Smad4", "-", "deficient", "embryos", "results", "from", "reduced", "cell", "proliferation", "rather", "than", "increased", "apoptosis", "." ]

[ 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Aggregation", "of", "mutant", "Smad4", "ES", "cells", "with", "wild", "-", "type", "tetraploid", "morulae", "rescues", "the", "gastrulation", "defect", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0 ]

[ "These", "results", "indicate", "that", "Smad4", "is", "initially", "required", "for", "the", "differentiation", "of", "the", "visceral", "endoderm", "and", "that", "the", "gastrulation", "defect", "in", "the", "epiblast", "is", "secondary", "and", "non", "-", "cell", "autonomous", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Rescued", "embryos", "show", "severe", "anterior", "truncations", ",", "indicating", "a", "second", "important", "role", "for", "Smad4", "in", "anterior", "patterning", "during", "embryogenesis", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Prevalence", "of", "p16", "and", "CDK4", "germline", "mutations", "in", "48", "melanoma", "-", "prone", "families", "in", "France", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0 ]

[ "The", "French", "Familial", "Melanoma", "Study", "Group", "." ]

[ 0, 0, 1, 2, 0, 0, 0 ]

[ "Germline", "mutations", "in", "the", "p16", "and", "CDK4", "genes", "have", "been", "reported", "in", "a", "subset", "of", "melanoma", "pedigrees", ",", "but", "their", "prevalence", "is", "not", "well", "known", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "We", "searched", "for", "such", "germline", "mutations", "in", "48", "French", "melanoma", "-", "prone", "families", "selected", "according", "to", "two", "major", "criteria", "families", "with", "at", "least", "three", "affected", "members", "(", "n", "=", "20", ")", "or", "families", "with", "two", "affected", "members", ",", "one", "of", "them", "affected", "before", "the", "age", "of", "50", "(", "n", "=", "28", ")", ",", "and", "one", "additional", "minor", "criterion", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Sixteen", "different", "p16", "germline", "mutations", "were", "found", "in", "21", "families", ",", "while", "one", "germline", "mutation", ",", "Arg24His", ",", "was", "detected", "in", "the", "CDK4", "gene", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "frequency", "of", "p16", "gene", "mutation", "in", "our", "sample", "(", "44", "%", ")", "is", "among", "the", "highest", "rates", "yet", "reported", "and", "the", "CDK4", "mutation", "is", "the", "second", "mutation", "detected", "in", "this", "gene", "worldwide", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "summary", ",", "our", "results", "show", "frequent", "involvement", "of", "the", "p16", "gene", "in", "familial", "melanoma", "and", "confirm", "the", "role", "of", "the", "CDK4", "gene", "as", "a", "melanoma", "-", "predisposing", "gene", ".", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0 ]

[ "Progression", "of", "somatic", "CTG", "repeat", "length", "heterogeneity", "in", "the", "blood", "cells", "of", "myotonic", "dystrophy", "patients", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0 ]

[ "The", "genetic", "basis", "of", "myotonic", "dystrophy", "(", "DM", ")", "is", "the", "expansion", "of", "an", "unstable", "CTG", "repeat", "in", "the", "34", "UTR", "of", "the", "DM", "protein", "kinase", "gene", "on", "chromosome", "19", "." ]

[ 0, 0, 0, 0, 1, 2, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0 ]

[ "One", "of", "the", "principal", "features", "of", "the", "DM", "mutation", "is", "an", "extraordinarily", "high", "level", "of", "somatic", "mosaicism", ",", "due", "to", "an", "extremely", "high", "degree", "of", "somatic", "instability", "both", "within", "and", "between", "different", "tissues", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "This", "instability", "appears", "to", "be", "biased", "towards", "further", "expansion", "and", "continuous", "throughout", "the", "life", "of", "an", "individual", ",", "features", "that", "could", "be", "associated", "with", "the", "progressive", "nature", "of", "the", "disease", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Although", "increasing", "measured", "allele", "size", "between", "patients", "clearly", "correlates", "with", "an", "increased", "severity", "of", "symptoms", "and", "an", "earlier", "age", "of", "onset", ",", "this", "correlation", "is", "not", "precise", "and", "measured", "allele", "length", "cannot", "be", "used", "as", "an", "accurate", "predictor", "of", "age", "of", "onset", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "order", "to", "further", "characterize", "the", "dynamics", "of", "DM", "CTG", "repeat", "somatic", "instability", ",", "we", "have", "studied", "repeat", "length", "changes", "over", "time", "in", "111", "myotonic", "dystrophy", "patients", "with", "varying", "clinical", "severity", "and", "CTG", "repeat", "size", "over", "time", "intervals", "of", "1", "-", "7", "years", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "We", "have", "found", "a", "direct", "progression", "of", "the", "size", "heterogeneity", "over", "time", "related", "to", "initial", "CTG", "repeat", "size", "and", "the", "time", "interval", "and", "always", "biased", "towards", "further", "expansion", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Attempts", "to", "mathematically", "model", "the", "dynamics", "have", "proved", "only", "partially", "successful", "suggesting", "that", "individual", "specific", "genetic", "and", "/", "or", "environmental", "factors", "also", "play", "a", "role", "in", "somatic", "mosaicism", ".", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Aspartylglucosaminuria", "among", "Palestinian", "Arabs", "." ]

[ 1, 0, 0, 0, 0 ]

[ "Aspartylglucosaminuria", "(", "AGU", ")", "is", "a", "rare", "disorder", "of", "glycoprotein", "metabolism", "caused", "by", "the", "deficiency", "of", "the", "lysosomal", "enzyme", "aspartylglucosaminidase", "(", "AGA", ")", "." ]

[ 1, 0, 1, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0, 0, 1, 2, 2, 2, 2, 2, 0, 0, 0, 0 ]

[ "AGU", "is", "inherited", "as", "an", "autosomal", "recessive", "trait", "and", "occurs", "with", "a", "high", "frequency", "in", "Finland", "because", "of", "a", "founder", "effect", "." ]

[ 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "While", "very", "few", "patients", "with", "AGU", "have", "been", "reported", "from", "non", "-", "Finnish", "origin", ",", "we", "diagnosed", "the", "disorder", "in", "8", "patients", "originating", "from", "3", "unrelated", "families", ",", "all", "Palestinian", "Arabs", "from", "the", "region", "of", "Jerusalem", "." ]

[ 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "clinical", "diagnosis", "of", "AGU", "is", "often", "difficult", ",", "in", "particular", "early", "in", "the", "course", "of", "the", "disease", ",", "and", "most", "of", "the", "patients", "are", "diagnosed", "after", "the", "age", "of", "5", "years", "." ]

[ 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "However", ",", "since", "these", "patients", "excrete", "early", "large", "amounts", "of", "aspartylglucosamine", "in", "urine", ",", "biochemical", "screening", "is", "easy", "by", "urine", "chromatography", ".", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Detection", "of", "heterozygous", "carriers", "of", "the", "ataxia", "-", "telangiectasia", "(", "ATM", ")", "gene", "by", "G2", "phase", "chromosomal", "radiosensitivity", "of", "peripheral", "blood", "lymphocytes", "." ]

[ 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "In", "ataxia", "-", "telangiectasia", "(", "A", "-", "T", ")", "patients", ",", "mutations", "in", "a", "single", "gene", ",", "ATM", ",", "result", "in", "an", "autosomal", "recessive", "syndrome", "that", "embraces", "a", "variety", "of", "clinical", "features", "and", "manifests", "extreme", "radiosensitivity", "and", "a", "strong", "pre", "-", "disposition", "to", "malignancy", "." ]

[ 0, 1, 2, 2, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0 ]

[ "Heterozygotes", "for", "the", "ATM", "gene", "have", "no", "clinical", "expression", "of", "A", "-", "T", "but", "may", "be", "cancer", "prone", "with", "a", "moderate", "increase", "in", "in", "vitro", "radiosensitivity", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "We", "performed", "a", "blind", "chromosomal", "analysis", "on", "G2", "-", "phase", "lymphocytes", "from", "7", "unrelated", "A", "-", "T", "patients", ",", "13", "obligate", "A", "-", "T", "heterozygotes", "(", "parents", "of", "the", "patients", ")", ",", "and", "14", "normal", "controls", "following", "X", "-", "irradiation", "with", "1", "Gy", "in", "order", "to", "evaluate", "this", "cytogenetic", "method", "as", "a", "tool", "for", "detection", "of", "ATM", "carriers", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Both", "A", "-", "T", "homozygotes", "and", "heterozygotes", "showed", "significantly", "increased", "levels", "of", "radiation", "-", "induced", "chromatid", "damage", "relative", "to", "that", "of", "normal", "controls", "." ]

[ 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "These", "results", "show", "that", "the", "G2", "-", "phase", "chromosomal", "radiosensitivity", "assay", "can", "be", "used", "for", "the", "detection", "of", "A", "-", "T", "heterozygotes", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0 ]

[ "In", "combination", "with", "molecular", "genetic", "analyses", ",", "this", "test", "may", "be", "of", "value", "in", "studies", "of", "familial", "and", "sporadic", "cancers", "aimed", "at", "determination", "of", "the", "potential", "involvement", "of", "ATM", "mutations", "in", "tumor", "risk", "or", "development", ".", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0 ]

[ "Ataxia", "-", "telangiectasia", ":", "identification", "and", "detection", "of", "founder", "-", "effect", "mutations", "in", "the", "ATM", "gene", "in", "ethnic", "populations", "." ]

[ 1, 2, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "To", "facilitate", "the", "evaluation", "of", "ATM", "heterozygotes", "for", "susceptibility", "to", "other", "diseases", ",", "such", "as", "breast", "cancer", ",", "we", "have", "attempted", "to", "define", "the", "most", "common", "mutations", "and", "their", "frequencies", "in", "ataxia", "-", "telangiectasia", "(", "A", "-", "T", ")", "homozygotes", "from", "10", "ethnic", "populations", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0 ]

[ "Both", "genomic", "mutations", "and", "their", "effects", "on", "cDNA", "were", "characterized", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Protein", "-", "truncation", "testing", "of", "the", "entire", "ATM", "cDNA", "detected", "92", "(", "66", "%", ")", "truncating", "mutations", "in", "140", "mutant", "alleles", "screened", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "The", "haplotyping", "of", "patients", "with", "identical", "mutations", "indicates", "that", "almost", "all", "of", "these", "represent", "common", "ancestry", "and", "that", "very", "few", "spontaneously", "recurring", "ATM", "mutations", "exist", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Assays", "requiring", "minimal", "amounts", "of", "genomic", "DNA", "were", "designed", "to", "allow", "rapid", "screening", "for", "common", "ethnic", "mutations", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "These", "rapid", "assays", "detected", "mutations", "in", "76", "%", "of", "Costa", "Rican", "patients", "(", "3", ")", ",", "50", "%", "of", "Norwegian", "patients", "(", "1", ")", ",", "25", "%", "of", "Polish", "patients", "(", "4", ")", ",", "and", "14", "%", "of", "Italian", "patients", "(", "1", ")", ",", "as", "well", "as", "in", "patients", "of", "Amish", "/", "Mennonite", "and", "Irish", "English", "backgrounds", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "Additional", "mutations", "were", "observed", "in", "Japanese", ",", "Utah", "Mormon", ",", "and", "African", "American", "patients", "." ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

[ "These", "assays", "should", "facilitate", "screening", "for", "A", "-", "T", "heterozygotes", "in", "the", "populations", "studied", ".", "." ]

[ 0, 0, 0, 0, 0, 0, 1, 2, 2, 0, 0, 0, 0, 0, 0, 0 ]