Deletion atChromosome16pI3.3as a CauseofRubinstein- TaybiSyndrome: Clinical Aspects

Summary Intheaccompanying paper,achromosomal localization oftheRubinstein-Taybi syndrome bycytogenetic investigations withfluorescence insitu hybridization techniques atchromosome 16pl3.3 isdescribed. We investigated 19ofthese patients andtheir parents(a) toascertain theparental origin ofthechromosome with thedeletion infamilies where such adeletion wasdetected, (b) todisclose whether uniparental disomy plays a role inetiology, and(c) tocompareclinical features inpatients with adeletion tothose inindividuals inwhom deletions werenotdetectable. Molecular studies showed a copyofchromosome 16fromeach parentinall 19 patients. Uniparental disomy wasalso excluded forfive other chromosome armsknown tobeimprinted inmice. Noneoftheprobes used fordetermining theorigin ofthedeleted chromosome proved tobeinformative. The clinical features wereessentially the sameinpatients withandwithout visible deletion, with apossible exception fortheincidence ofmicrocephaly, angulation ofthumbs andhalluces, andpartial duplication ofthehalluces. A small deletion at16pi3.3 may befound insome patients withRubinstein-Taybi syndrome. Cytogenetically undetectable deletions, point mutations, mosaicism, heterogeneity, orphenocopy byanongenetic causearethe mostprobable explanations fortheabsence ofcytogenetic ormolecular abnormalities inother patients with Rubinstein-Taybi syndrome.