IDENTIFICATION OF GENES FROM A 500-KB REGION AT 7Q11.23 THAT IS COMMONLY DELETED IN WILLIAMS-SYNDROME PATIENTS

Williams syndrome (WS) is a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Hemizygosity of the el astin (ELN) gene can account for the vascular and connective tissue ab normalities observed in WS patients, but the genes that contribute to features such as infantile hypercalcemia, dysmorphic facies, and menta l retardation remain to be identified, In addition, the size of the ge nomic interval commonly deleted in NS patients has not been establishe d In this study we report the characterization of a 500-kb region that was determined to be deleted in our collection of WS patients, A deta iled physical map consisting of cosmid, P1 artificial chromosomes, and yeast artificial chromosomes was constructed and used for gene isolat ion experiments. Using the techniques of direct cDNA selection and gen omic DNA sequencing three known genes (ELN, LIMK1, and RFC2), a novel gene (WSCR1) with homology to RNA-binding proteins, a gene. with homol ogy to restin, and four other putative transcription units were identi fied. LIMK1 is a protein kinase with two repeats of the LIM/double zin c finger motif, and it is highly expressed in brain. RFC2 is the 40-kD a ATP-binding subunit of replication factor C, which is known to play a role in the elongation of DNA catalyzed by DNA polymerase delta and epsilon. LIMK1 and WSCR1 may be particularly relevant when explaining cognitive defects observed in WS patients. (C) 1996 Academic Press, In c.