Findings appearing in NEJM also suggest different levels of impairment.
A multinational group of investigators say that an aberration in a particular region of human chromosome 1q21.1 appears to be associated with a variety of developmental disorders in children. Some people who have the aberration are only slightly affected or even unaffected, while others are more seriously impaired, they point out.
The scientists observed that the aberration can manifest itself as unexplained mild or moderate mental retardation, growth retardation, learning disabilities, seizures, autism, heart defects, other congenital abnormalities, cataracts, small head size, unusual facial features, hand deformities, or skeletal problems.
The scientists explain that the genomic structure of 1q21.1 is extremely complex. There are 15 assembly gaps, or 700 kb of missing sequence in 1q21.1, in the most recent map of the human genome. These gaps, they note, may contain as yet unknown genes that contribute to the differences in the types of developmental abnormalities that occur in children with the deletion. Supposedly unaffected deletion carriers might in fact have more subtle disorders that could be found during further clinical evaluations. For example, an examination of one apparently unaffected carrier revealed mild cataracts and a heart defect that were previously undetected.
The research group recognizes that the diversity of disorders and the lack of a distinct syndrome accompanying 1q21.1 rearrangements will complicate genetic diagnosing and counseling. Keeping in mind the many possible repercussions of having this rearrangement in the chromosome, they suggest that young carriers should be monitored over the long term for the emergence of learning disabilities, autism, schizophrenia, or other neuropsychiatric disorders.
The investigators used cytogenetic arrays to test people to determine the presence or absence of submicroscopic imbalances in small sections of their chromosomes. They checked for the presence of microdeletions and microduplications in a specific region of chromosome 1q21.1 in groups of patients with unexplained mental retardation, autism, or congenital abnormalities. The findings were compared to a control group of 4,737 controls.
No microdeletions were found in the control group. Two controls had one small duplication at the far end of the region under study, and only one had duplication of the entire region.
The research is published in the September 11 issue of the New England Journal of Medicine.