title: A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart.
abstract: Down syndrome is a major cause of mental retardation and congenital heart defects. While most of the affected individuals have three copies of chromosome 21, patients with partial trisomy 21 have also been described. These rare cases define a minimal region for the Down syndrome phenotype encompassing about 3 Mb around D21S55. By using a new method for the identification of coding sequences (Alu-splice PCR) we have identified a new gene, DSCR1, from region 21q22.1-q22.2. DSCR1 encodes a novel protein which has an acidic domain, a serine-proline motif, a putative DNA binding domain and a proline-rich region with the characteristics of a SH3 domain ligand. These features suggest that DSCR1 could be involved in transcriptional regulation and/or signal transduction. DSCR1 is highly expressed in human brain and heart, and increased expression in the brains of young rats compared with adults suggests a role for DSCR1 during central nervous system development. Structural characteristics, together with its particular expression in brain and heart, encourage us to suggest that the overexpression of DSCR1 may be involved in the pathogenesis of Down syndrome, in particular mental retardation and/or cardiac defects.
authors.affiliation: Molecular Genetics Department, Hospital Duran i Reynals, L'Hospitalet de Liobregat, Barcelona, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Fuentes
authors.forename: M A
authors.initials: MA
authors.lastname: Pritchard
authors.forename: A M
authors.initials: AM
authors.lastname: Planas
authors.forename: A
authors.initials: A
authors.lastname: Bosch
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000375:Aging / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002891:Chromosomes, Human, Pair 21; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004314:Down Syndrome / Q000196:embryology / Q000235:genetics*; D005091:Exons; D015870:Gene Expression; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011392:Proline / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D051381:Rats; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D011506:Proteins; C108612:RCAN1 protein, human; D011392:Proline