Further study of genetic interactions: Loss of short arm material in patients with ring chromosome 4 changes developmental pattern of del(4)(q33)

Segment 4q33 is not considered a probable location of a gene related with limb deficiency by Roberts and Tabin [Am J Hum Genet 55:1–6, 1994]; however, the occurrence of ectrodactyly or its equivalents in at least 9 published cases of monosomy 4q33 suggests probable location of one of these genes in that region. Ulnar ray defects and/or ectrodactyly were the prevailing forms. An additional loss of the tip of 4p in patients with ring chromosome 4 leads to a change of limb deficiency type: 8 of 9 patients with r(4) and limb deficiency had radial ray defects. Therefore, interactions between a proposed ½ dose “ectrodactyly” gene on 4q33 and some ½ dosage genes on distal 4p (or disturbed cellular homeostasis due to a ring chromosome 4) can change the developmental pattern of limb deficiency. Possible mechanisms and significance of the Phenomenon are discussed. © Wiley‐Liss, Inc.