Distinct 15q genotypes in Russell-Silver and ring 15 syndromes.

ABSTRACT

Individuals with a ring 15 chromosome [r(15)] and those with Russell-Silver syndrome have short stature, developmental delay, triangular face, and clinodactyly. To assess whether the apparent phenotypic overlap of these conditions reflects a common genetic cause, the extent of deletions in chromosome 15q was determined in 5 patients with r(15), 1 patient with del 15q26.1-qter, and 5 patients with Russell-Silver syndrome. All patients with Russell-Silver syndrome were diploid for genetic markers in distal 15q, indicating that Russell-Silver syndrome in these individuals was unlikely to be related to the expression of single alleles at these or linked genetic loci. At least 3 distinct sites of chromosome breakage close to the telomere were found in the r(15) and del 15q25.1-qter patients, with 1 r(15) patient having both a terminal and an interstitial deletion. Although the patient with del 15q25.1-qter exhibited the largest deletion and the most profound growth retardation, the degree of growth impairment among the r(15) patients was not correlated with the size of the deleted interval. Rather, the parental origin of the ring chromosome in several patients was associated with phenotypes that are also seen in patients with either Prader-Willi (PWS) or Angelman (AS) syndromes, conditions that result from uniparental expression of genes on chromosome 15. In fact, unequal representation of chromosome 15 alleles in 1 patient with r(15) suggests the possibility that a mosaic karyotype composed of the constitutional cell line and cell line(s) possibly deficient in the ring chromosome might be present. The PWS-like or AS-like phenotypes could be explained by postzygotic loss of the ring chromosome, leading to uniparental inheritance of the intact chromosome in some tissues of r(15) patients.