NOVEL HUMAN GENE FKBP6 IS DELETED IN WILLIAMS-SYNDROME

Williams syndrome (WS) is a developmental disorder caused by haploinsu fficiency of genes at 7q11.23. We have shown that hemizygosity of elas tin is responsible for one feature of WS,supravalvular aortic stenosis . We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. Here w e identify and characterize a novel gene, FKBP6, within the common WS deletion region. FKBP6 shows homology to the FK-506 binding protein (F KBP) class of immunophilins. FKBP6 has a putative N-terminal FK-506 bi nding and peptidylproyl isomerase (rotamase) domain and, like known hi gh-molecular-weight FKBPs, an imperfect C-terminal tetratricopeptide r epeat domain. FKBP6 is expressed in testis, heart, skeletal muscle, li ver, and kidney. FKBP6 consists of nine exons and is completely contai ned within a 35-kb cosmid clone. Fluorescence in situ hybridization ex periments show that FKBP6 gene is deleted in 40/40 WS individuals. Hem izygous deletion of FKBP6 may contribute to certain defects such as hy percalcemia and growth delay in WS. (C) 1998 Academic Press.