The breakpoints of seven interstitial de-letions of the long arm of chromosome 16 and two ring chromosomes of this chromosome were mapped by in situ hybridisation or by analysis of mouse/ human somatic cell hybrids containing the deleted chromosome 16. Use of a high resolution cytogenetic based physical map of chromosome 16 enabled breakpoints to be assigned to an average resolution of at least [1][2][3][4][5][6] Mb.In general, interstitial deletions involving q12 or q22.1 have broadly similar phenotypes though there are differences in specific abnormalities. Deletions involving regions more distal, from 16q22.1 to 16q24.1, were associated with relatively mild dysmorphism. One region of the long arm, q24.2 to q24.3, was not involved in any deletion, either in this study or in any previous report. Presumably, monosomy for this region is lethal. In contrast, patients with deletions of 16q21 have a normal phenotype. These results are consistent with the proposed distribution of genes, frequent in telomeric Giesma light band regions but infrequent in G positive bands. (_J Med Genet 1993;30:828-32 The breakpoints of IDI and 1D3-ID5 were mapped by Southern blot or PCR analysis of mouse/human somatic cell hybrids containing the deleted chromosome.'7 The presence (+) or absence (-) of a DNA marker on the chromosome 16 with a deletion was determined by FISH except in cases indicated by an asterisk where this was determined by inheritance of polymorphic (AC)n microsatellite markers. The order of DNA markers is from centromere to qter. showed head circumference and height at the 25th centile for age and weight at the 3rd centile for age. She had a flat occiput and right epicanthic fold but otherwise was not dysmorphic. Re-examination at 71 years showed a short, microcephalic girl with minor dysmorphism consisting of recessed hairline, slightly prominent broad forehead, supernumerary nipple (present in her normal mother), short and broad big toes, and small nails on the fifth toes. She was retarded, not toilet trained, and had general learning difficulties. Patient ID7. This female was delivered spontaneously at 37 weeks' gestation. Birth weight was 3170 g (50th to 75th centile),length 48 cm (50th centile), and head circumference 34 cm (75th centile). During the first few months there was normal feeding and development. At 8 weeks, clinical examination showed trembling, hypertonia, narrow palpebral fissures with antimongoloid slant, broad nasal root, flat forehead, an extremely large anterior fontanelle, long philtrum, high arched palate, and evidence of micrognathia. The two lower incisors were present at birth (both lost spontaneously at 4 weeks), the ears were low set and dysmorphic, there were flexion defects of the middle fingers, and widely spaced nipples. A photograph of the patient is presented in fig 1. DNA markersDeletions and rings

We report on 4 sibs (2F, 2M) with Prader-Willi syndrome (PWS). Diagnosis was made clinically on the basis of history, behavior, and physical findings in 3 of the sibs. The other child had died at age 10 months with a history and clinical findings typical of first phase of PWS. Results of chromosome studies on the parents and surviving sibs were normal. The implications of this unusual familial occurrence for our understanding of PWS are discussed.

No abstract

The proband was born when the mother was 27 and the father 32 after a normal pregnancy and delivery. The parents and an older brother are healthy with normal karyotypes. At 13j years she had severe mental and physical retardation, general muscular hypotonia, hyperactivity, and trichotillomania. Height and weight were below the 3rd centile, ossification was delayed, and she had brachycephaly, a wide fontanelle, deep-seated ears, hypertelorism, and antimongoloid slants. Bilateral cleft lip and palate had been treated surgically. Hands and feet were short, Dubois sign was positive, there was bilateral clinodactyly, and syndactyly between fingers 2 and 3, and more markedly between toes 2, 3, and 4. There were single transverse palmar creases on both hands and diastasis of the rectus abdominis muscle. X-ray examination showed asymmetry of the os sacrum and spina bifida occulta. Chronic constipation, gastrooesophageal reflux, and disturbed micturition were reported. The external genitalia were normal, no testes were palpable, and there was no onset of puberty.G banding of the proband's lymphocytes revealed an aberrant chromosome 9 which is interpreted as an inverted tandem ('mirror') duplication of 9p (figure a). Of 100 metaphases investigated, 97 showed, in addition to a single X chromosome, a small acrocentric chromosome which was identified as a Y by Q and C banding and distamycin A pretreatment' (figure b, d). Presence of Y heterochromatin specific repeated sequences was confirmed by Hae III restriction endonuclease analysis of the DNA of the proband, father, and brother. The remaining three metaphases lacked a Y chromosome. After staining preparations of the proband with quinReceived for publication 9 March 1981 Short reports acrine mustard, C banding showed an extremely large block of constitutive heterochromatin in one chromosome 7 (figure c). This particular chromosome was also seen in the mother and brother. Using a cytotoxicity assay technique, the proband was found to be negative for the H-Y antigen.The karyotype of the proband is therefore 45,XO,inv dup(9)(pter-p24 p21 p24 p21 -qter)/46,XY,inv dup(9)(pter --p24 p21 -)p24 p21 --qter). Trisomy 9p could not be confirmed by gene dosage measurements (eg galactose-1-P-uridyl transferase), nor could the internal genitalia be explored, since the proband's parents refused any further examination. However, the phenotype of the proband clearly shares features with previously reported cases of XY gonadal dysgenesis2 and trisomy 9p.