A 343 Italian cohort of patients analysed with array-comparative genomic hybridization: unsolved problems and genetic counselling difficulties.
Array-CGH spots a clear genetic cause in roughly one-fifth of Italian patients with ID or autism, echoing similar yields worldwide.
01Research in Context
What this study did
Doctors in Italy ran array-CGH on 343 children and adults who had intellectual disability, autism, or both.
Array-CGH is a blood test that scans the whole genome for missing or extra chunks of DNA.
The team wanted to know how often the test finds a clear genetic cause for the patient’s delays.
What they found
The scan picked up a definite or likely genetic change in 22% of the patients.
About four out of five of those changes were brand-new variants that scientists still don’t fully understand.
Even with modern tools, telling parents “why” remains hard in most cases.
How this fits with other research
Hutchins et al. (2020) ran the same test on 90 Italian girls with autism and got the same 22% hit rate.
The close match shows the number is solid inside Italy’s health system.
Al-Mamari et al. (2015) saw a slightly higher 27% yield in families where parents are related, proving ancestry can nudge the rate upward.
Duerden et al. (2012) found 24% in a U.S. clinic, so the tool works across countries too.
Hong et al. (2021) dropped to only 11% when they looked at non-syndromic ID without autism, reminding us that the more complex the picture, the more likely array-CGH will help.
Why it matters
If you work with kids who have both autism and intellectual disability, expect array-CGH to give a clear genetic answer about one time in five.
When the result comes back as a “variant of unknown significance,” you can tell families that this happens to most patients and that science is still catching up.
Use the 22% figure when you counsel families and when you write justification for insurance approval.
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02At a glance
03Original abstract
BACKGROUND: The recent introduction of microarrays for genetic analyses has allowed higher etiological diagnostic rates in patient with intellectual disability (ID), autism spectrum disorders (ASD), epilepsy and multiple congenital anomalies (MCA), because of its resolution. This approach still results of high complexity and some limitations have been reported. In fact, it discloses several variants of unknown significance (VOUS) or incidental findings. In all cases, a massive amount of data is generated, because of this, the analysis and the interpretation is very difficult and often without a definitive conclusion. METHOD: We analysed an Italian cohort of 343 patients with ID, MCA and ASD by array-comparative genomic hybridization. The purpose of this work was to consider the proportion of the chromosomal abnormalities in such cohort and to assess the distribution of the different type of the chromosomal abnormalities concerning their pathogenic significance, their origin and their correlation to these clinical phenotypes. RESULTS: Array-comparative genomic hybridization analysis revealed 76 positive results. Abnormalities were detected in 27.8% of patients with ID, 11.1% with ASD, 10.7% with epilepsy and 19.4% with multiple congenital anomalies. The anomalies were classified in three major groups: group 1 (27 patients) with pathogenic alterations (P group); group 2 (34 patients) with VOUS potentially pathogenic (PP group); and group 3 (13 patients) with VOUS potentially benign (PB group). As expected, comparing the diagnostic groups, we observed a greater number of deletions in the P group and that all the abnormalities of the PB group were inherited. CONCLUSIONS: Our retrospective study resulted in confirming the high detection rate of microarrays. CNV classification remains a complex procedure. The difficulty in CNV classification points out the importance of the patient selection, helping the interpretation of the molecular cytogenetic results.
Journal of intellectual disability research : JIDR, 2021 · doi:10.1111/jir.12867