PARTIAL MONOSOMY OF CHROMOSOME 1P36.3 - CHARACTERIZATION OF THE CRITICAL REGION AND DELINEATION OF A SYNDROME

We describe 5 patients ranging in age from 3 to 47 years, with karyoty pic abnormalities resulting in monosomy for portion of 1p36.3, microce phaly, mental retardation, prominent forehead, deep-set eyes, depresse d nasal bridge, flat midface, relative prognathism, and abnormal ears, Four patients have small hands and feet, All exhibited self-abusive b ehavior, Additional findings in some of the patients include brain ano malies, optic atrophy, hearing loss and skeletal deformities, The brea kpoints within chromosome 1 were designated at 1p36.31 (3 cases), 1p36 .32 (1 case) and 1p36.33 (1 case), Thus, the smallest region of deleti on overlap is lp36.33-->1 pter. Detection of the abnormal 1 relied on high resolution G-band analysis, Fluorescence in situ hybridization (F ISH) utilizing a DNA probe (Oncor D1Z2) containing the repetitive sequ ences in distal 1p36, confirmed a deletion of one 1 homologue in all 5 cases, The abnormal 1 resulted from a de novo deletion in only one pa tient, The remaining patients were either confirmed (3 cases) or suspe cted (I case) to have unbalanced translocations. Despite the additiona l genetic imbalance present in these four cases, monosomy of 1p36.33 a ppears to be responsible for a specific clinical phenotype, Characteri zation of this phenotype should assist in the clinical diagnosis of th is chromosome abnormality. (C) 1995 Wiley-Liss, Inc.