Further refinement of COL4A1 and COL4A2 related cortical malformations.

Abstract

Mutations in COL4A1 have been reported in schizencephaly and porencephaly combined with microbleeds or calcifications, often associated with ocular and renal abnormalities, myopathy, elevated creatine kinase levels and haemolytic anaemia. In this study, we aimed to clarify the phenotypic spectrum of COL4A1/A2 mutations in the context of cortical malformations that include schizencephaly, polymicrogyria and/or heterotopia.

METHODS:

We screened for COL4A1/A2 mutations in 9 patients with schizencephaly and/or polymicrogyria suspected to be caused by vascular disruption and leading to a cerebral haemorrhagic ischaemic event. These included 6 cases with asymmetrical or unilateral schizencephaly and/or polymicrogyria and 3 cases with bilateral schizencephaly.

RESULTS:

One de novo missense COL4A1 mutation (c.3715 G > A, p.(Gly1239Arg)) and two COL4A2 mutations were found, respectively in one familial case (c.4129G > A, p.(Gly1377Arg)) and one sporadic patient (c.1776+1G > A). In three other cases, COL4A1 variants of unknown significance were identified. None of our patients demonstrated neuromuscular or hematological anomalies. Brain malformations included a combination of schizencephaly, mainly asymmetrical, with porencephaly or ventriculomegaly (3/3 mutated patients). We did not observe microbleeds or microcalcifications in any of our cases, hence we do not believe that they represent a distinctive feature of COL4A1/A2 mutations.

CONCLUSIONS:

Our study further emphasizes the need to search for both COL4A1 and COL4A2 mutations in children presenting with uni- or bilateral polymicrogyria with schizencephaly, even in the absence of intracranial microbleeds, calcification or associated systemic features.

• Authors: Mara Cavallin, Manuele Mine, Marion Philbert, Nathalie Boddaert, Jean Marie Lepage, Thibault Coste, Vanessa Lopez-Gonzalez, Maria Jose Sanchez-Soler, Maria Juliana Ballesta-Martínez, Ganaëlle Remerand, Laurent Pasquier, Agnès Guët, Jamel Chelly, Karine Lascelles, Carol Prieto-Morin, Manoelle Kossorotoff, Elisabeth Tournier Lasserve, Nadia Bahi-Buisson
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 61 Issue 12 Pg. 765-772 (Dec 2018) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 30315939 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier Masson SAS.

Chemical References

• COL4A1 protein, human
• COL4A2 protein, human
• Collagen Type IV

Topics

• Child
• Child, Preschool
• Collagen Type IV (genetics)
• Female
• Humans
• Infant
• Magnetic Resonance Imaging
• Male
• Mutation
• Polymicrogyria (diagnostic imaging, genetics, physiopathology)
• Porencephaly (diagnostic imaging, genetics, physiopathology)
• Schizencephaly (diagnostic imaging, genetics, physiopathology)