Intellectual disability update Jan 2018

Gene: NFIA

Comment when marking as ready: Three unrelated cases with variants / deletions involving this gene and a relevant phenotype.

Created: 8 Mar 2018, 3:22 p.m.

Comment on list classification: Three unrelated cases with NFIA variants (1 frameshifting SNV and 2 intragenic deletions; involving exons 4-9 and exons 1-2). Phenotypes reported include delayed psychomotor development / developmental delay, in association with other features (mainly renal). On balance this reaches the threshold for inclusion and supports a LOF mechanism.

Created: 8 Mar 2018, 3:22 p.m.

Comment on list classification: Three unrelated cases in the literature to specifically support NFIA causing Brain malformations with or without urinary tract defects (ID being part of the clinical phenotype).

Created: 5 Mar 2018, 5:43 p.m.

Comment on phenotypes: Associated to CHROMOSOME 1P32-P31 DELETION SYNDROME, INCLUDED Weining Lu et al., (2007) PMID: 17530927.

Created: 5 Mar 2018, 5:34 p.m.

Although the publications referenced are all for the single gene NFIA causing Brain malformations with or without urinary tract defects some patients with a similar phenotype have larger deletions of chromosome 1p32-p31, including the NFIA gene; this disorder thus represents a contiguous gene deletion syndrome.

Created: 5 Mar 2018, 5:30 p.m.

added tag deletions. Currently only pathogenic deletion variants are reported for this gene.

Created: 5 Mar 2018, 5:16 p.m.

Comment on publications: Rao et al. (2014) PMID: 24462883 identified a de novo heterozygous 120-kb intragenic deletion for BRMUTD . Negishi et al. (2015) PMID: 27081522 identified a de novo heterozygous 1-bp deletion (c.1094delC, NM_001134673.3) in the NFIA gene, resulting in a frameshift and premature termination (Pro365HisfsTer32)
and Nyboe et al. (2015) 25714559- in a family (4 affecteds) they identified heterozygosity for a 109-kb intragenic deletion (chr1.61,497,698-61,607,171, GRCh37) that affected exons 1 and 2 of the NFIA gene

Created: 5 Mar 2018, 5:15 p.m.