ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
22031302 254 kb deletion of NFIA in a patient with hydrocephalus and hypoplasia of corpus collosum and other features.
24462883 Rao et al. 2014: Describes a de novo, intragenic deletion of NFIA exons 4-9 in an 8-year-old female with features similar to other patients with larger 1p31.1 deletions, including hypoplastic corpus callosum, ventriculomegaly, developmental delay, dysmorphic features, and genitourinary tract anomalies. No functional studies were performed. No exonic deletions were seen in the authors' review of DGV or 1000 Genomes data. This patient also had metopic craniosynostosis, a feature not previously associated with haploinsufficiency of NFIA or deletions of the larger 1p31.1 region.
27081522 Negishi et al. (2015) describe a five-year-old male with a de novo truncating variant (c.1094delC; p.Pro365Hisfs*32) in NFIA identified via whole exome sequencing. The boy was described as having polymicrogyria in the right frontal lobe, interhemispheric cysts, ventricular enlargement and callosal agenesis (identified via MRI of the brain), as well as cystectasia, left hydronephrosis, bilateral grade IV vesicoureteral reflux, and non-progressive enlargement of head circumference.

Haploinsufficiency phenotype comments:

Several other patients with larger deletions involving the 1p31.1 region, including NFIA and other genes, have been reported with similar features, including hypoplastic corpus callosum, ventriculomegaly, genitourinary tract anomalies, macrocephaly, etc. (PMIDs 17530927, 19763616, and others).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity