We present the clinical and laboratory findings in an institutionalised adult patient originally referred for autism. A high risk of colorectal cancer was predicted when an interstitial deletion of the long arm of chromosome 5, del(5) (q15q22.3), was detected in her lymphocytes and deletion of the MCC and APC genes confirmed by molecular analysis. Adenomatous polyposis coli and carcinoma of the rectum were subsequently diagnosed in the patient. She was profoundly mentally retarded, autistic, and had minor dysmorphic features consistent with those of previous patients with similar deletions.The deletion arose as a result of recombination within the small insertion loop formed at meiosis by the direct insertion (dir ins(5) (q22.3ql4.2ql5)) found in the patient's mother. This family further confirms the cytogenetic mapping of both MCC and APC genes to 5q22 and comparison with other recent cases suggests that both genes and their closely linked markers lie within the 5q22.1 subband.

We analyzed 448 independently ascertained reciprocal translocations and 220 inversions referred to our diagnostic laboratory. Twenty-eight percent of the translocations and 8.5% of the inversions arose de novo, the proportion being influenced by the method of ascertainment. It was highest, 47%, among translocations ascertained through an abnormal phenotype. With the exception of the 3:1 unbalanced segregants, the remainders were equally likely to have been paternally or maternally inherited. The segregation from balanced translocation and inversion carriers showed an equal number of offspring with a normal chromosome constitution and with a balanced rearrangement. The number of unbalanced segregants among the translocations was 2.7% where the proband was balanced, and 19.2% where the proband was unbalanced. There was only a single unbalanced inversion. A search for recurring translocations showed only the well documented t(11;22) to occur with unusual frequency in our series and those of others, and we concluded that the few other translocations that were seen on more than one occasion were likely to be identical by descent (IBD). Similarly the majority of the recurring inversions, with the exception of "common variants," seemed likely to be IBD. However, eight inversions recurred in our data and in most other series and may well be genuine independent rearrangements. A search of the known olfactory receptor (OR) loci and duplicons suggested that such sequences did not form an important contribution to the breakpoints of recurring rearrangements detected by light microscopy.

We report on 2 girls with small de novo terminal deletions of the long arm of chromosome 2 and breakpoints within q37. Four cases with similar or more extensive deletions have been previously reported in full. Hypotonia and psychomotor retardation were the only manifestations common to all 6 cases. The phenotype associated with small terminal 2q deletions is variable and clearly not always as mild as indicated in previous reports. The abnormality may also be more common than has been assumed.