Cornelia de Lange syndrome (CDLS) is a developmental malformation syndrome characterized by mental handicap, limb reduction defects, distinctive facial features and growth retardation. Most patients have hearing impairment and a considerable number have congenital heart defects and gastrointestinal abnormalities. Classical cases show a spectrum of limb abnormalities ranging from miniaturization to absence of fingers and arms. In a few rare cases CDLS patients are found to have severe deficiency of upper and lower limbs. Usually, however, absence of limbs and digits is confined to the upper limbs, although the feet are usually short with post-axial shortening of the toes in post-pubertal individuals. Patients typically present as sporadic cases but dominant inheritance is indicated in some rare multicase pedigrees. Associated chromosomal abnormalities have provided the only real clues to subchromosomal gene localization, notably two patients with balanced, de novo translocations: t(3;17)(26q.3; 23q.1) and t(14;21)(q32;q11). Of these the breakpoint at 3q26.3 has been considered to be of particular interest because of phenotypic overlap with the duplication 3q syndrome whose critical region is 3q26.3–q27. We show, however, that in some families the disease does not segregate with 3q26-q27 markers, suggesting the possibility of genetic heterogeneity. We have developed YAC/BAC contigs and cloned regions spanning the translocation breakpoints at 3q26.3 and 21q11. We will report on analyses of genes at both breakpoints and screening of candidate CDLS genes.
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|Published - Nov 2000