Application of ELN cosmid probes using fluorescence in situ hybridization (FISH) towards a clinical diagnostic test for Williams syndrome

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133419

Lowery, M; Brothman, L; Leonard, C ^[1]

---

1. Univ. of Utah Health Center, Salt Lake City, UT (United States); and others

Williams syndrome (WS) is characterized by mental deficiency, gregarious personalities, dysmorphic facies, supravalvular aortic stenosis (SVAS), and idiopathic infantile hypercalcemia. Expression of the phenotype is variable. Deletions including an elastin allele (ELN) are thought to be the basis of the connective tissue and vascular abnormalities in WS patients. Patients with WS are hemizygous for ELN, exhibiting a submicroscopic deletion at 7q11.23 detected by FISH. To substantiate the hemizygosity hypothesis and define molecular cytogenetics in patients with familial and sporadic WS, a series of 71 patients were evaluated. EBV-transformed lymphocytes from 48 selected patients were cultured and harvested according to cytogenetic protocol. Cosmids containing ELN were biotinylated and hybridized to metaphase cells by routine procedures. In addition, an alpha-satellite probe for chromosome 7 was included in hybridizations as an internal control. Thirty-one of these 48 patients (65%) showed a deletion in one ELN allele by FISH. Negative patients were shown to be non-affected family members or patients in the {open_quotes}uncertain{close_quotes} category (expressing some, but not all features characteristic of WS). The FISH data were consistent with molecular analyses of ELN deletions. Twenty-three additional patients were referred to confirm or rule out a diagnosis of WS. Nine patients (39%) showed a deletion of ELN by FISH. Correlations between phenotype and FISH results are in progress. These results suggest that a rapid, accurate diagnostic technique for WS using FISH can be implemented in the cytogenetics laboratory as a routine clinical service. Identification of the deletion in patients suspected of having WS will facilitate classification of these patients and improve clinical management.

• OSTI ID: 133419
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
CONGENITAL MALFORMATIONS
DIAGNOSIS
DNA
DNA HYBRIDIZATION
FLUORESCENCE
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 7
MENTAL DISORDERS
PATIENTS
PHENOTYPE
PROBES