DELETION OF THE ENTIRE NF1 GENE DETECTED BY FISH - 4 DELETION PATIENTS ASSOCIATED WITH SEVERE MANIFESTATIONS

Genetic analysis of NF1 has indicated a wide diversity of mutations, i ncluding chromosome rearrangements, deletions, insertions, duplication s, and point mutations, Recently, five severely affected individuals h ave been found by Kayes et al, [1994] to have deletions encompassing t he entire gene, These deletions were detected by quantitative Southern analysis, To simplify deletion detection, we have employed fluorescen ce in situ hybridization (FISH) using intragenic probes, Thirteen unre lated individuals with NF1 have been studied, Among six with severe ma nifestations, four have been found to have deletions detected by probe s cFF13, cFB5D, cP5, yA43A9, yA113D7 and yD8F4, All four deletion pati ents have severe developmental delay, minor and major anomalies (inclu ding one with bilateral iris colobomas), and multiple cutaneous neurof ibromas or plexiform neurofibromas which were present before age 5 yea rs, FISH provides a simple and rapid means of identification of NF1 ge ne deletions and will allow more rigorous testing of the hypothesis th at such deletions are associated with severe manifestations. (C) 1995 Wiley-Liss, Inc.