title: Prenatal diagnosis of ATR-X syndrome in a fetus with a new G>T splicing mutation in the XNP/ATR-X gene.
abstract: The molecular cause of the alpha-thalassemia/mental retardation syndrome (ATR-X) resides in mutations affecting the XNP/ATR-X gene. Recently molecular defects in the gene have been found in singular cases of a discrete number of X-linked mental retardation (XLMR). ATR-X-affected males are characterised by severe mental retardation, distinct facial dysmorphisms and genital abnormalities, besides a wide spectrum of pathological features and an extremely limited biological fitness. Given that molecular investigation of XNP/ATR-X mutations is made onerous by the length of the gene transcript, we carried out a prenatal diagnosis in a fetus at risk for ATR-X syndrome by initially determining the XNP/ATR-X gene haplotype before considering gene sequencing. Disease-associated haplotype analysis was performed selecting five genic (CA)n repeats that showed high heterozygosity (Het>0.7) in the general population. The fetus segregated an identical allelic pattern to that of the affected child of the family under investigation who shows features suggestive of the ATR-X syndrome. Subsequent mutational analysis of the gene revealed a novel IVS3+1G>T splicing mutation confirming the diagnosis.
authors.affiliation: Laboratorio di Patologia Genetica, IRCCS Oasi Maria SS, Troina, EN, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Fichera
authors.forename: M
authors.initials: M
authors.lastname: Silengo
authors.forename: A
authors.initials: A
authors.lastname: Spalletta
authors.forename: M L
authors.initials: ML
authors.lastname: Giudice
authors.forename: C
authors.initials: C
authors.lastname: Romano
authors.forename: A
authors.initials: A
authors.lastname: Ragusa
mesh_terms: D000328:Adult; D004265:DNA Helicases; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing; D013577:Syndrome; D014960:X Chromosome; D000075924:X-linked Nuclear Protein; D017085:alpha-Thalassemia / Q000150:complications / Q000175:diagnosis* / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D022821:RNA Splice Sites; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein