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• W2898850951 abstract "The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly. The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly." @default.
• W2898850951 created "2018-11-09" @default.
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• W2898850951 date "2018-11-01" @default.
• W2898850951 modified "2023-10-15" @default.
• W2898850951 title "NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly" @default.
• W2898850951 cites W1602386717 @default.
• W2898850951 cites W1808711893 @default.
• W2898850951 cites W1921704775 @default.
• W2898850951 cites W1964746292 @default.
• W2898850951 cites W1970413157 @default.
• W2898850951 cites W1975373361 @default.
• W2898850951 cites W1979795014 @default.
• W2898850951 cites W1980740976 @default.
• W2898850951 cites W1982720718 @default.
• W2898850951 cites W1996769957 @default.
• W2898850951 cites W2004773203 @default.
• W2898850951 cites W2005009098 @default.
• W2898850951 cites W2007943561 @default.
• W2898850951 cites W2008713605 @default.
• W2898850951 cites W2009521014 @default.
• W2898850951 cites W2009999837 @default.
• W2898850951 cites W2014760588 @default.
• W2898850951 cites W2020158301 @default.
• W2898850951 cites W2020887683 @default.
• W2898850951 cites W2021891225 @default.
• W2898850951 cites W2022722148 @default.
• W2898850951 cites W2027473402 @default.
• W2898850951 cites W2031188085 @default.
• W2898850951 cites W2032588195 @default.
• W2898850951 cites W2034263202 @default.
• W2898850951 cites W2036841261 @default.
• W2898850951 cites W2038181219 @default.
• W2898850951 cites W2046095073 @default.
• W2898850951 cites W2059145105 @default.
• W2898850951 cites W2064358322 @default.
• W2898850951 cites W2068211965 @default.
• W2898850951 cites W2074748130 @default.
• W2898850951 cites W2085198610 @default.
• W2898850951 cites W2088487912 @default.
• W2898850951 cites W2090263938 @default.
• W2898850951 cites W2092041178 @default.
• W2898850951 cites W2105320166 @default.
• W2898850951 cites W2105693920 @default.
• W2898850951 cites W2109181132 @default.
• W2898850951 cites W2112282280 @default.
• W2898850951 cites W2113054914 @default.
• W2898850951 cites W2117344609 @default.
• W2898850951 cites W2117719082 @default.
• W2898850951 cites W2117950559 @default.

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