REGIONAL FINE MAPPING OF THE BETA-CRYSTALLIN GENES ON CHROMOSOME-22 EXCLUDES THESE GENES AS PHYSICALLY LINKED MARKERS FOR NEUROFIBROMATOSISTYPE-2

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disease, c haracterized by the development of bilateral vestibular schwannomas. T he NF2 gene has been assigned to chromosome 22. Cataract and other eye abnormalities are frequently seen in NF2 patients. The specific assoc iation of eye abnormalities and NF2 might be caused by a genetic chang e on chromosome 22 that affects both the NF2 gene and a physically lin ked crystallin gene. In order to test this hypothesis, we regionally l ocalized the known crystallin genes (i.e. CRYBB2, CRYB82P1, CRYBB3, an d CRYBA4) on chromosome 22. Crystallin gene-specific probes were hybri dized to an extended panel of human x rodent somatic cell hybrids cont aining various portions of chromosome 22. It was found that all crysta llin genes map to a very small region on chromosome 22 that is physica lly separate from the NF2 gene region by at least 160 kb of DNA. In ad dition, we found that the betaB crystallin genes (CRYBB2, CRYBB2P1, an d CRYBB3) are clustered on a 300 kb SacII fragment and that the betaA4 crystallin gene (CRYBA4) is not part of this cluster. We conclude tha t the ocular manifestations in many NF2 patients are probably not the primary consequence of rearrangements on chromosome 22 that involve bo th the NF2 gene and a nearby beta crystallin gene. (C) 1993 Wiley-Liss , Inc.