Human Disease Model Report: NFIA-related disorder

General Information

Name

NFIA-related disorder

FlyBase ID

FBhh0001368

Disease Ontology Term

NFIA-related disorder

Parent Disease

OMIM

BRAIN MALFORMATIONS WITH OR WITHOUT URINARY TRACT DEFECTS; BRMUTD

Overview

NFIA-related disorder is an autosomal dominant disease usually caused by haploinsufficiency of the NFIA gene. A missense mutation of NFIA found in two patients with phenotypic features of NFIA haploinsufficiency has been characterized to determine if it represents a loss-of-function variant. NFIA encodes a member of the NF1 (nuclear factor 1) family of transcription factors. There is an orthologous gene in Drosophila, NfI, but it has not been used in the context of this disease model.

Multiple UAS constructs of the human Hsap\NFIA gene have been introduced into flies, including wild-type and a gene carrying the disease-implicated missense variant (K125E); see the 'Disease-Implicated Variants' table, below. Expression of the wild-type human gene in neuronal tissues causes lethality or phenotypic defects. Neuronal expression of the K125E variant has no effect; none of the dominant effects of NFIA expression were observed for the missense allele.

[updated Jun. 2021 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: NFIA-related disorder

OMIM report

[BRAIN MALFORMATIONS WITH OR WITHOUT URINARY TRACT DEFECTS; BRMUTD](https://omim.org/entry/613735)

Human gene(s) implicated

[NUCLEAR FACTOR I/A; NFIA](https://omim.org/entry/600727)

Symptoms and phenotype

NFIA-related disorder comprises central nervous system abnormalities (most commonly abnormalities of the corpus callosum) with or without urinary tract defects, such as unilateral or bilateral vesicoureteral reflux and hydronephrosis. Additional features include macrocephaly, seizures, developmental delay and/or cognitive impairment, nonspecific dysmorphic features, ventriculomegaly, and hypotonia, which can exacerbate motor delay and feeding issues in infancy. [Gene Reviews, NFIA-Related Disorder; 2021.06.29]

(FlyBase Curators, 2013-)

Genetics

Brain malformations with or without urinary tract defects (BRMUTD) is caused by heterozygous mutation in the NFIA gene. Some patients with a similar phenotype have larger deletions of chromosome 1p32-p31, including the NFIA gene. [from MIM:613735; 2021.06.29]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

NFIA encodes a member of the NF1 (nuclear factor 1) family of transcription factors. [Gene Cards, NFIA; 2021.06.29]

(FlyBase Curators, 2013-)

External links