Dr. Heather C. Mefford, acting assistant professor of Paediatrics at the University of Washington, and Dr. Andrew J. Sharp of the University of Geneva Medical School in Switzerland say 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.
While some people having the aberration are only slightly affected or apparently unaffected, others are more seriously impaired.
For their study, the group used cytogenetic arrays, recent technological advances that can determine the presence or absence of submicroscopic imbalances in small sections of chromosomes.
The researchers said that 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, and compared their findings with similar testing of a group from the general population.
While they did not find any microdeletions in 4,737 controls from the general population, two controls had a small duplication at the far end of the region under study, and only one had duplication of the entire region.
Published in the New England Journal of Medicine, the study report suggests that the genomic structure of 1q21.1 is extremely complex. The research article further states that there are still 15 assembly gaps, or 700 kb of missing sequence in 1q21.1, in the most recent map of the human genome.
The researchers say that these gaps 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.
Given that other research groups have also found a connection between 1q21.1 deletions and schizophrenia in some people and parts missing in the reproductive tract in other people, the researchers say that their study confirms the association of 1q21.1 rearrangements with a broad spectrum of disorders, and also further dispel the notion that such rearrangements will necessarily follow the one-gene, one-disease model.
The authors recognize that the diversity of disorders and the lack of a distinct syndrome accompanying 1q21.1 rearrangements will complicate genetic diagnosing and counselling.
They suggest that doctors who are caring for patients with unexplained developmental abnormalities consider the identification of a 1q21.1 rearrangement in a patient a significant clinical finding, and probably an influential genetic factor contributing to the patient's disorder.
According to them, young carriers should be monitored over the long term for the emergence of learning disabilities, autism, schizophrenia, or other neuropsychiatric disorders.
The authors say that this study adds 1q21.1 as a chromosomal locus to the growing list of structural variants that might eventually be included in genetic screening panels for people with developmental delays or neuropsychiatric diagnoses.
"Counseling in the prenatal setting will present the greatest challenge: although the likelihood of an abnormal outcome is high in a person with a 1q21.1 rearrangement, current knowledge does not allow us to predict which abnormality will occur in any given person," they write.