DISTINCT 15Q GENOTYPES IN RUSSELL-SILVER AND RING-15 SYNDROMES

Individuals with a ring 15 chromosome [r(15)] and those with Russell-S ilver syndrome have short stature, developmental delay, triangular fac e, and clinodactyly. To assess whether the apparent phenotypic overlap of these conditions reflects a common genetic cause, the extent of de letions in chromosome 15q was determined in 5 patients with r(15), 1 p atient with del 15q26.1-qter, and 5 patients with Russell-Silver syndr ome, All patients with Russell-Silver syndrome were diploid for geneti c markers in distal 15q, indicating that Russell-Silver syndrome in th ese 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 termina l and an interstitial deletion, Although the patient with del 15q25.1- qter exhibited the largest deletion and the most profound growth retar dation, the degree of growth impairment among the r(15) patients was n ot correlated with the size of the deleted interval, Rather, the paren tal origin of the ring chromosome in several patients was associated w ith phenotypes that are also seen in patients with either Prader-Willi (PWS) or Angelman (AS) syndromes, conditions that result from unipare ntal expression of genes on chromosome 15. In fact, unequal representa tion of chromosome 15 alleles in 1 patient with r(15) suggests the pos sibility that a mosaic karyotype composed of the constitutional cell l ine and cell line(s) possibly deficient in the ring chromosome might b e present, The PWS-like or AS-like phenotypes could be explained by po stzygotic loss of the ring chromosome, leading to uniparental inherita nce of the intact chromosome in some tissues of r(15) patients. (C) 19 96 Wiley-Liss, Inc.