X-LINKED NEURODEGENERATIVE SYNDROME WITH CONGENITAL ATAXIA, LATE-ONSET PROGRESSIVE MYOCLONIC ENCEPHALOPATHY AND SELECTIVE MACULAR DEGENERATION, LINKED TO XP22.33-PTER

Linkage analysis was performed in a previously described family segreg ating for an X-linked progressive neurological disorder [Bertini et al ., 1992]. In three generations, the disease was inherited from the mot hers in seven affected males (Fig, 1), Five had severe congenital hypo tonia and died during the first year of life. Two other boys (maternal cousins) were found to have severe congenital ataxia, late-onset prog ressive myoclonic encephalopathy, and selective macular degeneration; brain CT-scan showed moderate cerebellar vermis hypoplasia. Linkage an alysis was carried out in 12 informative relatives using 35 microsatel lite markers (Genethon) evenly distributed on the X chromosome. A mult ipoint analysis showed a significant linkage (Z > 2) between the disea se and three markers in the Xp22.33 region: DYS403 (Z = 2.37, theta = 0) which maps in the pseudoautosomal region, DXS7099 (Z = 2.45, theta = 0), and DXS7100 (Z = 2.48, theta = 0). Further Linkage analysis with more telomeric markers will refine the location of this severe X-link ed encephalopathy. (C) 1996 Wiley-Liss, Inc.