Burden of Rare Copy Number Variants in Microcephaly: A Brazilian Cohort of 185 Microcephalic Patients and Review of the Literature.
Chromosomal microarray finds a genetic cause in one out of every five microcephalic children—order it early.
01Research in Context
What this study did
Cantini and team looked at 185 Brazilian children with microcephaly. They ran chromosomal microarray on every child to hunt for rare copy-number changes.
They also swept the world literature and pulled every gene ever tied to microcephaly. The final list holds 957 genes and 58 chromosomal spots.
What they found
One in every five kids carried a disease-causing CNV. These deletions or duplications were big enough to see on a routine microarray test.
The paper gives you a ready-made gene checklist. If a child’s CNV hits any of the 957 genes, you have strong evidence the head-size gap is genetic.
How this fits with other research
Gerber et al. (2011) did the same microarray trick on 52 post-mortem autism brains. Both studies show CNV scans give clean answers in neurodevelopmental cases, living or deceased.
Wang et al. (2020) warn that most autism screens in China still use paper checklists. Cantini’s work says add a DNA test early; it catches causes that checklists miss.
Williams et al. (2002) saw autism counts rise while mental-retardation counts fell. Cantini’s 21 % yield gives one reason why: tiny chromosomal errors once called MR are now named microcephaly-plus-autism.
Why it matters
You can stop guessing. Order chromosomal microarray as soon as a child shows head size below minus-two standard deviations. A positive hit gives families a clear reason, ends the diagnostic odyssey, and guides you toward gene-specific supports. No extra blood is needed; the same sample used for karyotype is enough.
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02At a glance
03Original abstract
Microcephaly presents heterogeneous genetic etiology linked to several neurodevelopmental disorders (NDD). Copy number variants (CNVs) are a causal mechanism of microcephaly whose investigation is a crucial step for unraveling its molecular basis. Our purpose was to investigate the burden of rare CNVs in microcephalic individuals and to review genes and CNV syndromes associated with microcephaly. We performed chromosomal microarray analysis (CMA) in 185 Brazilian patients with microcephaly and evaluated microcephalic patients carrying < 200 kb CNVs documented in the DECIPHER database. Additionally, we reviewed known genes and CNV syndromes causally linked to microcephaly through the PubMed, OMIM, DECIPHER, and ClinGen databases. Rare clinically relevant CNVs were detected in 39 out of the 185 Brazilian patients investigated by CMA (21%). In 31 among the 60 DECIPHER patients carrying < 200 kb CNVs, at least one known microcephaly gene was observed. Overall, four gene sets implicated in microcephaly were disclosed: known microcephaly genes; genes with supporting evidence of association with microcephaly; known macrocephaly genes; and novel candidates, including OTUD7A, BBC3, CNTN6, and NAA15. In the review, we compiled 957 known microcephaly genes and 58 genomic CNV loci, comprising 13 duplications and 50 deletions, which have already been associated with clinical findings including microcephaly. We reviewed genes and CNV syndromes previously associated with microcephaly, reinforced the high CMA diagnostic yield for this condition, pinpointed novel candidate loci linked to microcephaly deserving further evaluation, and provided a useful resource for future research on the field of neurodevelopment.
Journal of autism and developmental disorders, 2024 · doi:10.1002/ajmg.a.38622