Truncating mutation in NFIA causes brain malformation and urinary tract defects

Abstract

Chromosome 1p32-p31 deletion syndrome involving the Nuclear factor I/A (NFIA) gene is characterized by corpus callosum hypoplasia or defects and urinary tract defects. Herein we report on a case resembling the 1p32-p31 deletion syndrome carrying a de novo truncating mutation (c.1094delC; p.Pro365Hisfs*32) in the NFIA gene, confirming that haploinsufficiency of the NFIA gene is a major determinant of this syndrome.

Figure 1

Head MRI, voiding cysturethrogram (VCUG) and craniofacial appearance of our patient. (a) Axial T2-weighted image showing interhemispheric cysts, ventricular enlargement and polymicrogyria (arrow). (b) Mid-sagittal T1-weighted image showing callosal agenesis (asterisk). (c) The VCUG showed bilateral grade IV vesicoureteral reflux. (d) Representative photograph of the patient showing a little dysmorphic facial features including mild macrocephaly, high forehead, and thin upper lip. His parents gave informed consent for publication of this image.

Figure 2

Genetic analysis of the pedigree. (a) Family tree of the pedigree. (b) Filtering the candidate mutations. Numbers show the patient result. The top numbers indicate number of called variants by whole-exome sequencing. The second numbers indicate number of variants after filter out known variants in databases, except for those which were also known pathogenic mutations. The third number indicates number of variants after excluded synonymous change variants. The bottom numbers indicate number of variants consistent with the phenotype in the pedigree (that is, total of the de novo, autosomal recessive, X-linked and compound heterozygous variants). Finally, only one deletion variant was remained. (c) Identified frameshift mutation in the NFIA gene. (d) Sanger sequencing of the NFIA mutation. Patient had a heterozygous c.1094delC mutation (arrow) not found in his parents.