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

• DOI: 10.1007/s004390050961
• Publication Date: 2002-08-25T04:52:48Z
• Authors: H. Z. Ring; H. Chang; Angèle Gu...; Alexis Brice; Eric LeGuern; Uta Francke
• Keywords: Adult; Genetic Markers; Male; 0301 basic medicine; Base Sequence; Genetic Linkage; Molecular Sequence Data; Chromosome Mapping; Genes, Recessive; Exons; Ligands; Introns; Alternative Splicing; 03 medical and health sciences; Charcot-Marie-Tooth Disease; Chromosomes, Human, Pair 5; Humans; Female; Amino Acid Sequence; Chromosomes, Artificial, Yeast; Lung; Gene Library

Neuregulin-2 (NRG2) is a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ErbB family of receptors, neuregulin-2 induces the growth and differentiation of epithelial, neuronal, glial and other types of cells. In this study, we have cloned the human neuregulin-2 gene, and determined its genomic structure and alternative splicing patterns. By using radiation hybrid mapping panels, the human NRG2 gene was mapped to the D5S658-D5S402 region within 5q23-q33, close to an autosomal recessive form of demyelinating Charcot-Marie-Tooth (CMT) disease. The NRG2 gene was found to be on two yeast artificial chromosomes overlapping the candidate interval and was, thus, considered a good positional candidate 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 nucleotide polymorphisms were identified in the NRG2 gene. Genotyping in two families localized the NRG2 gene outside of the revised candidate interval between D5S402-D5S210 and excluded NRG2 as the gene responsible for this form of CMT disease.