ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.