Chromosome region 1q21.1 contains extensive and complex low-copy repeats, and copy number variants (CNVs) in this region have recently been reported in association with congenital heart defects1, developmental delay2,3, schizophrenia and related psychoses4,5. We describe 21 probands with the 1q21.1 microdeletion and 15 probands with the 1q21.1 microduplication. These CNVs were inherited in most of the cases in which parental studies were available. Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively. Notably, a paralog of the HYDIN gene located on 16q22.2 and implicated in autosomal recessive hydrocephalus6 was inserted into the 1q21.1 region during the evolution of Homo sapiens7; we found this locus to be deleted or duplicated in the individuals we studied, making it a probable candidate for the head size abnormalities observed. We propose that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies. These phenotypes are subject to incomplete penetrance and variable expressivity.
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Some authors are based in the Department of Molecular and Human Genetics at Baylor College of Medicine (BCM), which offers extensive genetic laboratory testing, including use of arrays for genomic copy number analysis, and derives revenue from this activity.
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Brunetti-Pierri, N., Berg, J., Scaglia, F. et al. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat Genet 40, 1466–1471 (2008). https://doi.org/10.1038/ng.279
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