An eight-case 1q21 region series: novel aberrations and clinical variability with new features.
Eight new autism cases show that 1q21 chromosome changes bring extra skeletal and brain-stem traits—order microarray when you see autism plus dysmorphology.
01Research in Context
What this study did
Chezan et al. (2019) mapped eight new cases of 1q21 chromosome changes. All clients had autism plus intellectual disability. The team used microarray scans to spot the exact DNA gains and losses. They listed each person’s medical and behavioral traits to build a picture of the syndrome.
What they found
Every client carried a different 1q21 deletion or duplication. Most had extra traits not seen before: odd skull shape, spine curves, and brain-stem signs. The paper gives clinicians a fuller checklist to watch for when 1q21 shows up on a lab report.
How this fits with other research
Al-Mamari et al. (2015) tested a larger autism group and found microarray hits in 27 % of cases. Their data extend this paper by showing the real-world pick-up rate when you order the test. Demily et al. (2018) warn that one rare copy-number variant can hide a second one. Their 22q11 case series urges you to order full gene panels even after the first finding, a step C et al. did not address. Konstantareas et al. (1999) linked 2q37 loss to a distinct autism look. Both studies use the same case-series style and remind you to think “chromosome first” when dysmorphic features meet severe ASD.
Why it matters
If your client has autism plus unusual facial or skeletal signs, ask the doctor about chromosomal microarray. A 1q21 result tells you the cause is genetic, not poor parenting or bad luck. You can stop hunting for hidden allergies or elusive toxins. Instead, write goals that fit known 1q21 strengths and limits, and teach the family that future siblings might need early screening.
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02At a glance
03Original abstract
BACKGROUND: Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings. METHODS: Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1-6 in RBM8A. RESULTS: Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889-kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12). CONCLUSION: Although the deletion in case 5 did not include the thrombocytopenia-absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia-absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype-phenotype correlations for this region.
Journal of intellectual disability research : JIDR, 2019 · doi:10.1111/jir.12592