Novel COL4A1 mutation in a fetus with early prenatal onset of schizencephaly

Abstract

Porencephaly and schizencephaly are congenital brain disorders that can be caused by COL4A1 mutations, though the underlying mechanism and developmental processes are poorly understood. Here, we report a patient with schizencephaly, detected by fetal ultrasonography and fetal magnetic resonance imaging, with a de novo novel mutation in COL4A1 (c.2645_2646delinsAA, p.Gly882Glu). Our results suggest that the onset of damage that potentially results in schizencephaly occurs mid-pregnancy.

Novel CUL7 biallelic mutations alter the skeletal phenotype of 3M syndrome

“…6 Intractable Disease Center, Saitama Medical University Hospital, Saitama, Japan. 7 Department of Radiology, Kanagawa Children's Medical Center, Yokohama, Japan…”

“…Targeted resequencing was performed for the affected patient. Genomic DNA captured by the TruSight One Sequencing Panel (Illumina, San Diego, CA, USA) was sequenced on the MiSeq platform (Illumina) with 151base pair paired-end reads as previously described 7 . Candidate variants were confirmed by Sanger sequencing.…”

Periventricular Venous Infarction in an Extremely Premature Infant as the Cause of Schizencephaly

“…3 Schizencephaly is a heterogeneous condition and can develop as a result of genetic and acquired causes in early neuroembryogenesis, many of them being of vascular disruptive nature. [1][2][3][4][5][6][7][8] Rapid evolution of molecular biology, genetics, and imaging has led to the understanding that schizencephaly is not a malformation secondary to abnormal cortical organi-zation or focal cortical dysplasia as suggested earlier and the earlier agenesis hypothesis has been shifted in favor of an encephaloclastic process. 1 Furthermore, it is believed that both schizencephaly and porencephaly are caused by the same encephaloclastic process and can only be distinguished based on the time of insult.…”

“…In contrast, porencephaly is the result of stroke after completion of neuronal migration and leads to lesions without the gray matter lining of the cleft. 7,8 Prenatal vascular events result in destructive brain lesions that are genetic or infectious in origin; however, in many cases the origin is unknown. 7 The COL4A1 and COL4A2 gene mutations have been reported in relation to a broad spectrum of cerebrovascular diseases and are also the most frequent genetic mutations seen in schizencephaly and porencephaly.…”

“…7 The COL4A1 and COL4A2 gene mutations have been reported in relation to a broad spectrum of cerebrovascular diseases and are also the most frequent genetic mutations seen in schizencephaly and porencephaly. 2,7 However, only a few cases have provided clear evidence of the development of schizencephaly after fetal stroke 8,9 and, to the best of our knowledge, no case report has described this sequence of events after neonatal periventricular venous infarction (PVI).…”