We report on an infant with a previously undescribed chromosome 15 deletion (q26.1----qter) and compare the clinical findings with those of 7 reported patients with deletions of distal 15q, as well as ring chromosome 15 syndrome patients. Most of the patients with deletions of distal 15q, including our patient, have intrauterine growth retardation (IUGR), microcephaly, abnormal face and ears, micrognathia, highly arched palate, renal abnormalities, lung hypoplasia, failure to thrive, and developmental delay/mental retardation. Several genes have been assigned to the 15q25----qter region, including insulin-like growth factor 1 receptor (IGF1R). DNA analysis from our patient documented the loss of one IGF1R gene copy. Our study further localizes the IGF1R gene distal to the 15q26.1 band. It is interesting to speculate that the severe IUGR and postnatal growth deficiency of our patient and other patients with similar chromosome 15 deletions are related to the loss of an IGF1R gene copy which may lead to an abnormal number and/or structure of the receptors.

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28S ribosomal RNA (rRNA) (2-4), suggesting that the absence of the human rRNA may be related to the loss of human chromosomes. It is not due to the absence of the human acrocentric chromosomes, which carry the structural genes for rRNA (5, 6), because Marshall et al. (4) found no human 28S rRNA in a large series of mousehuman hybrids that contained 2 to 11 human acrocentrics.The chromosome regions that carry the rRNA genes have been identified as the nucleolus organizer regions (NORs) (7), and these regions can be stained preferentially by the Ag-AS silver staining method (8). In human diploid cell cultures the Ag-AS method stains the short arm regions of most of the acrocentric chromosomes (9, 10). The NORs of the same human acrocentric chromosomes are not stained in a mouse-human hybrid that has lost some human chromosomes (11). There is no evidence to suggest that rRNA genes are deleted from the human acrocentrics in hybrid cells. Therefore the absence.of Ag-AS stain suggests that this method detects only chromosome regions that functioned as nucleolus organizers in the preceding interphase, and, by implication, produced rRNA.Somatic cell hybrids between either mouse peritoneal macrophages or mouse cells obtained from a teratocarcinoma and HT-1080 human fibrosarcoma cells retain human chromosomes and lose mouse chromosomes (12). If preferential chromosome elimination is closely correlated with preferential suppression of nucleolus organizer activity, these hybrids should express only human nucleolus organizer activity. This appears to be the case. METHODS BALB/c mouse peritoneal macrophages were obtained according to a modification of the procedure described by Cohn and Benson (13) and were fused with HT-1080-6TG human fibrosarcoma cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) (12) in the presence of f3-propiolactone-inactivated Sendai virus at pH 8.0 (14). The fused cultures were maintained in hypoxanthine-aminopterin-thymidine (HAT) selective medium (15). Large colonies of hybrid cells were visible 3-4 weeks after fusion. The colonies were picked and, subsequently, grown. OTT6050 mouse teratocarcinoma cells were obtained from a solid teratocarcinoma of a strain 129 mouse (16,17) by cutting in small fragments in trypsin/EDTA, resuspending in Eagle's minimal essential medium (MEM), and filtering through sterile gauze. The teratocarcinoma cells were fused with HT-1080-6TG cells in the presence of f.-propiolactone-inactivated Sendai virus. Hybrid colonies were selected in hypoxanthine-aminopterin-thymidine medium.Hybrid cells were maintained in Eagle's medium supplemented with 10% fetal calf serum. Mitotic cells were shaken from the culture flasks and transferred to a centrifuge tube containing 0.1 ml of colcemid (10 Ag/ml) for every 10 ml of medium and the tubes were centrifuged immediately at 800 rpm in an IEC clinical centrifuge for 7 min. The cell pellet was resuspended in 75 mM KCI. After 10 min the suspension was centrifuged and the cells were fixed for an hour in freshly prepa...

We report on 2 patients (3 1/2 year-old-male and 6-year-old female) with the ring 15 chromosome syndrome and speech delays and review 25 cases from the literature. The main characteristics of this syndrome include growth retardation (100%), variable mental retardation (95%), microcephaly (88%), hypertelorism (46%), and triangular facies (42%). Other frequent findings include delayed bone age (75%), brachydactyly (44%), speech delay (39%), frontal bossing (36%), anomalous ears (30%), café-au-lait spots (30%), cryptorchidism (30%), and cardiac abnormalities (30%). The average age at diagnosis was 8.1 years. The average maternal and paternal age at the time of birth was 28 and 31 years, respectively.

Nucleolus organizer regions were detected by the Ag-AS silver method in fixed metaphase chromosomes from human and primates. In the human, silver was deposited in the secondary constriction of a maximum of five pairs of acrocentric chromosomes: 13, 14, 15, 21 and 22. The chimpanzee also had five pairs of acrocentric chromosomes stained, corresponding to human numbers 13, 14, 18, 21 and 22. A gibbon had a single pair of chromosomes with a secondary constriction, which corresponded to the nucleolus organizer region. In each case the Ag-AS method detected the sites which have been shown by in situ hybridization to contain the ribosomal RNA genes. An orangutan had eight pairs of acrocentric chromosomes stained with Ag-AS, probably corresponding to human numbers 13, 14, 15, 18, 21 and 22, plus two others. Two gorillas had silver stain over two pairs of small acrocentric chromosomes and at the telomere of one chromosome 1. The larger gorilla acrocentric chromosomes had no silver stain although they all had secondary constrictions and entered into satellite associations.