Rare ACTG1 variants in fetal microlissencephaly
Karine Poirier1, Jelena Martinovic2, Annie Laquerrière3
1Inserm, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France.
European Journal of Medical Genetics
|July 19, 2015
Summary
Genetic testing using whole exome sequencing identified ACTG1 gene mutations in patients with microlissencephaly. This expands the known spectrum of Baraitser-Winter syndrome, suggesting ACTG1 as a key gene for diagnosing microlissencephaly.
Area of Science:
- Genetics
- Developmental Biology
- Neurology
Background:
- Baraitser-Winter cerebrofrontofacial syndrome is linked to heterozygous ACTG1 mutations.
- This syndrome presents with cortical malformations, specifically pachygyria with a severity gradient.
Observation:
- Whole exome sequencing was performed on 12 patients with prenatal microlissencephaly diagnoses.
- Two fetal cases and one living patient presented with missense mutations in the ACTG1 gene.
- Affected individuals exhibited microcephaly, facial dysmorphism (microretrognathia, hypertelorism, low-set ears), and brain malformations.
Findings:
- Brain malformations included lissencephaly with an immature cortical plate.
- Corpus callosum abnormalities (dysmorphic or absent) and vermian hypoplasia were observed in a significant proportion of cases.
- The study identified ACTG1 mutations in patients diagnosed with microlissencephaly.
Implications:
- Exome sequencing demonstrates significant diagnostic value for microlissencephaly cases.
- These findings may broaden the recognized malformation spectrum associated with ACTG1-related Baraitser-Winter syndrome.
- The ACTG1 gene is suggested for inclusion in genetic assessments for microlissencephaly.
