title: hGFRalpha-4: a new member of the GDNF receptor family and a candidate for NBIA.
abstract: Hallervorden-Spatz syndrome (neurodegeneration with brain iron accumulation type 1; OMIM entry 234200) is a rare inherited neurodegenerative disease. In this article, evidence for a newly identified gene as a candidate for Hallervorden-Spatz syndrome is given. Previously Hallervorden-Spatz syndrome was mapped to a 4-cm region in 20p12.3-13. During positional cloning efforts a new member of the glial-derived neurotrophic factor receptor family was discovered in this region. Like other members of this receptor family, this new gene is predicted to be secreted and glycosyl-phosphatidylinositol linked, and it maintains conserved cysteine residues. However, cDNA and genomic studies in both humans and mice indicate that this gene lacks the sequence corresponding to exons 2 and 3 in other family members. In situ hybridization reveals that it is expressed primarily in the brain and bladder in the embryonic mouse. Mutation analysis of patients with Hallervorden-Spatz syndrome revealed two potentially significant amino acid changes in two patients but failed to identify mutations in the remaining 10 subjects. The implication of these findings for the relationship between this gene and Hallervorden-Spatz syndrome is discussed.
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine and Pediatrics, University of California, San Francisco, California 94143, USA.
authors.forename: B
authors.initials: B
authors.lastname: Zhou
authors.forename: S K
authors.initials: SK
authors.lastname: Bae
authors.forename: A C
authors.initials: AC
authors.lastname: Malone
authors.forename: B B
authors.initials: BB
authors.lastname: Levinson
authors.forename: Y M
authors.initials: YM
authors.lastname: Kuo
authors.forename: M R
authors.initials: MR
authors.lastname: Cilio
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: S J
authors.initials: SJ
authors.lastname: Hayflick
authors.forename: J M
authors.initials: JM
authors.lastname: Gitschier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor
chemical_list: D029721:Drosophila Proteins; C491860:GFRA4 protein, human; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D007501:Iron; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila