FISH characterisation of an identical (16)(p11.2p12.2) tandem duplication in two unrelated patients with autistic behaviour

Partial trisomy 16p is a rare chromosomal anomaly in newborns: of the fewer than 30 carrier patients so far reported, most were born to parents with a balanced translocation involving the p arm of chromosome 16.1 Pure partial trisomy 16p has been reported in seven patients,2–6 three of whom (all showing behavioural problems with autistic traits) carried a tandem duplication of the (16)(p11.2–p12) region4,6; minor dysmorphisms were reported in only one patient.4 Linkage studies indicated chromosome 16p as a major location for autism susceptibility genes,7 while association was reported between autistic traits and attention deficit or hyperactivity disorders mapping to the 16p13 band.8 In addition TSC2, one of the genes responsible for tuberous sclerosis, a syndrome often associated with autistic traits, maps to the same cytogenetic band.9 We report the clinical phenotype and refined molecular cytogenetic characterisation of a patient carrying a (16)(p11.2p12.2) duplication. By extending the FISH analysis to a previously described patient with an apparently similar chromosomal rearrangement,6 we found that low copy repeats map to the 16p11.2 and 16p12.2 duplication endpoints, suggesting non-allelic homologous recombination as the pathogenetic mechanism. This finding is consistent with the non-random occurrence of the observed chromosomal rearrangement and the high frequency of segmental duplications identified throughout chromosome 16.10–12 We also inferred from genotype-phenotype correlation studies that genes involved in autism susceptibility are located within the duplicated region. Patient 1 is a 25 year old man, the first son of unrelated parents. At the time of his birth, his mother was aged 30 and his father 29 years. He was born at term with a weight of 2.550 kg (3rd centile). The father suffered from alcohol misuse and left the family when the patient was 12 years old. Because of …