Polymorphism of restriction fragment length in the detection of the precise status of monosomy 21 in a deformed retarded girl

The authors used genomic single copy DNA fragments cloned from chromosome 21 to study cytogenetic abnormalities in patients not easily defined by conventional cytogenetic means. Ten restriction fragment length polymorphisms (RLFP) detected by 8 independent probes were used to detect homologous sequences from chromosome 21 in genomic digests of DNA from one patient and her parents. The proband is a 3 1/2-year-old girl who was referred to us at 1 month of age because of hypertonia, hirsutism, flattened nasal bridge, antimongoloid slant of palpebral fissures, high arched palate and bilateral hip dysplasia. The karyotype of the proband was: 46, XX, -3, -21, + ? del (3) (3 pter----3q1:) +? (3qter----3q1:: 21q21----21 pter). GTG banding and the karyotype of her parents were normal (in peripheral blood and skin fibroblasts). She was re-examined by us every three months, because she showed physical and psychomotor retardation. We traced the inheritance of RFLPs from her parents, and familial molecular studies showed in contrast to the cytogenetic analysis that the patient is disomic for all regions of 21q tested by our collection of probes. The use of molecular technology has resulted in a more precise definition of 21 chromosome abnormalities and especially the "complete" monosomy 21 which is extremely rare in live born infants.