The human neuregulin-2 (NRG2) gene: cloning, mapping and evaluation as a candidate for the autosomal recessive form of Charcot-Marie Tooth disease linked to 5q

Neuregulin-2 (NRG2) is a novel member of the neuregulin family of growth an d differentiation factors. Through interaction with the ErbB family of rece ptors, neuregulin-2 induces the growth and differentiation of epithelial, n euronal, glial and other types of cells. In this study, we have cloned the human neuregulin-2 gene, and determined its genomic structure and alternati ve splicing patterns. By using radiation hybrid mapping panels, the human N RG2 gene was mapped to the D5S658-D5S402 region within 5q23-q33, close to a n autosomal recessive form of demyelinating Charcot-Marie-Tooth (CMT) disea se. The NRG2 gene was found to be on two yeast artificial chromosomes overl apping the candidate interval and was, thus, considered a good positional c andidate for this form of CMT. When the entire neuregulin-2 coding sequence and splice junctions were explored, however, no mutation was identified in one CMT family linked to 5q23-q33. In addition, three intronic single nucl eotide polymorphisms were identified in the NRG2 gene. Genotyping in two fa milies localized the NRG2 gene outside of the revised candidate interval be tween D5S402-D5S210 and excluded NRG2 as the gene responsible for this form of CMT di:;ease.