Identification and characterization of a highly conserved protein absent in the Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E) contiguous gene deletion syndrome (AMME)

We recently described a novel contiguous gene deletion syndrome (AMME) in X q22.3 that includes Alport syndrome (A), mental retardation (M), midface hy poplasia (RI), and elliptocytosis (E). While the Alport syndrome is due to deletion of the COL4A5 gene, no other genes are known in the region with th e exception of our recent finding of the FACIA gene. In our effort to isola te additional genes from the deleted region, we have identified the gene na med AMMECR1 (Alport syndrome, mental retardation, midface hypoplasia, and e lliptocytosis chromosomal region gene 1). RACE experiments and screening of cDNA libraries enabled us to obtain the entire ORF of the gene (1002 bp) f ollowed by about 2 kb of 3'UTR AMMECR1 is composed of six exons, shows a ub iquitous 6.5-kb transcript, and codes for a protein with a molecular mass o f 35.5 kDa. Sequence analysis revealed that this gene is conserved in sever al species ranging from Caenorhabditis elegans and yeast to micro-organisms . Exon 2 of AMMECR1 encodes a domain consisting of six amino acids identica lly conserved throughout the course of evolution and whose function is as y et unknown. Analysis of the predicted protein product using ExPAsy tools ra ises the possibility that the gene may code for a regulatory factor potenti ally involved in the development of AMME contiguous gene deletion syndrome. (C) 1999 Academic Press.