hGFRα-4: a new member of the GDNF receptor family and a candidate for NBIA

Zhou, Bing; Bae, Sylvia K; Malone, Amy C; Levinson, Barbara B; Kuo, Yien-Ming; Cilio, M.Roberta; Bertini, Enrico; Hayflick, Susan J; Gitschier, Jane M

« Previous Next »Pediatric Neurology
Volume 25, Issue 2 , Pages 156-161, August 2001

hGFRα-4: a new member of the GDNF receptor family and a candidate for NBIA

Bing Zhou, PhD
- Howard Hughes Medical Institute and Department of Medicine and Pediatrics; University of California; San Francisco, California, USA
Sylvia K Bae, BA
- Department of Molecular and Medical Genetics; Oregon Health Sciences University; Portland, Oregon, USA
Amy C Malone, BA
- Department of Molecular and Medical Genetics; Oregon Health Sciences University; Portland, Oregon, USA
Barbara B Levinson, MS
- Howard Hughes Medical Institute and Department of Medicine and Pediatrics; University of California; San Francisco, California, USA
Yien-Ming Kuo, PhD
- Howard Hughes Medical Institute and Department of Medicine and Pediatrics; University of California; San Francisco, California, USA
M.Roberta Cilio, MD
- Neurophysiology Unit; Bambino Gesus Children’s Hospital; 00165 Rome, Italy
Enrico Bertini, MD
- Neurophysiology Unit; Bambino Gesus Children’s Hospital; 00165 Rome, Italy
Susan J Hayflick, MD
- Department of Molecular and Medical Genetics; Oregon Health Sciences University; Portland, Oregon, USA
Jane M Gitschier, PhD
- Howard Hughes Medical Institute and Department of Medicine and Pediatrics; University of California; San Francisco, California, USA
- Communications should be addressed to: Dr. Gitschier; Howard Hughes Medical Institute and Department of Medicine and Pediatrics; University of California; San Francisco, CA94143

Received 26 September 2000; accepted 11 December 2000.

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.