DDG2P
Gene: FLNA
The DDG2P confidence category for the disease MELNICK-NEEDLES SYNDROME, OMIM:309350 is definitive. The allelic requirement and mutation consequence are monoallelic_X_het and uncertain (PMID:12612583). The DDG2P confidence category for the disease EPILEPTIC ENCEPHALOPATHY is definitive. The allelic requirement and mutation consequence are monoallelic_X_het and altered gene product structure (PMID:23934111). The DDG2P confidence category for the disease PERIVENTRICULAR NODULAR HETEROTOPIA TYPE 1, OMIM:300049 is definitive. The allelic requirement and mutation consequence are monoallelic_X_het and absent gene product (PMIDs: 11532987;11914408;16299064;14988809;23032111;9883725;20014127;8290091). The DDG2P confidence category for the disease Otopalatodigital Syndrome is definitive. The allelic requirement and mutation consequence are monoallelic_X_hem and altered gene product structure (PMIDs: 20301567;15654694;16596676;15940695;17632775;12612583;17431908). The DDG2P confidence category for the disease FRONTOMETAPHYSEAL DYSPLASIA, OMIM:305620 is definitive. The allelic requirement and mutation consequence are monoallelic_X_hem and altered gene product structure (PMIDs: 28498505;12612583). The DDG2P confidence category for the disease TERMINAL OSSEOUS DYSPLASIA, OMIM:300244 is definitive. The allelic requirement and mutation consequence are monoallelic_X_hem and absent gene product (PMIDs: 8644737;18854860;10982965;23037936). The DDG2P confidence category for the disease X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION, OMIM:300048 is definitive. The allelic requirement and mutation consequence are monoallelic_X_hem and increased gene product level (PMIDs: 8644737;18854860;23037936).Created: 4 Oct 2023, 5:08 p.m. | Last Modified: 4 Oct 2023, 5:08 p.m.
Panel Version: 3.12
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION, OMIM:300048; MELNICK-NEEDLES SYNDROME, OMIM:309350; Otopalatodigital Syndrome; PERIVENTRICULAR NODULAR HETEROTOPIA TYPE 1, OMIM:300049; TERMINAL OSSEOUS DYSPLASIA, OMIM:300244; FRONTOMETAPHYSEAL DYSPLASIA, OMIM:305620; EPILEPTIC ENCEPHALOPATHY
Publications
New gene:disorder association added to DDG2P, September 2019: PERIVENTRICULAR NODULAR HETEROTOPIA 1. Disease confidence rating in DDG2P: confirmed; DDG2P mutation consequence: loss of function. DDG2P mode of inheritance: x-linked dominant.Created: 3 Oct 2019, 10:30 a.m. | Last Modified: 3 Oct 2019, 10:30 a.m.
Panel Version: 1.109
Comment on mode of inheritance: DDG2P MOI is listed as hemizygous mosaic for Childhood Interstitial Lung Disease; x-linked dominant for EPILEPTIC ENCEPHALOPATHY; hemizygous for FG SYNDROME TYPE 2; x-linked dominant for MELNICK-NEEDLES SYNDROME; hemizygous for FRONTOMETAPHYSEAL DYSPLASIA; hemizygous for OTOPALATODIGITAL SYNDROME TYPE 1; hemizygous for OTOPALATODIGITAL SYNDROME TYPE 2; hemizygous for TERMINAL OSSEOUS DYSPLASIA; hemizygous for X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION. All disorders have a Confirmed Disease confidence rating.Created: 11 Jun 2019, 3:04 p.m.
DDG2P update, curated January 8th 2019: MOP for FRONTOMETAPHYSEAL DYSPLASIA changed from 'uncertain' to 'gain of function'.No MOP change curated in PanelApp, because mechanism is listed as loss of function for some (but not all) DD-G2P disorders.Created: 8 Jan 2019, 8:42 a.m.
Mosaicism tag added: In DD-G2P download, hemizygous,mosaic MOI listed for Childhood Interstitial Lung Disease.Created: 19 Nov 2018, 1:21 p.m.
Original DDG2P rating: confirmed (for all listed disorders). Multiple MOPs in DD-G2P download: all missense/in frame, loss of function, uncertain. Multiple MOIs in DD-G2P download: hemizygous, x-linked dominant and hemizygous,mosaic.Created: 19 Nov 2018, 11:29 a.m.
Publications for gene: FLNA were updated from 16299064; 20014127; 11532987; 11914408; 8290091; 9883725; 14988809 to 23934111; 16596676; 8644737; 20301567; 11914408; 16299064; 11532987; 9883725; 28498505; 10982965; 20014127; 23032111; 17632775; 17431908; 23037936; 18854860; 15654694; 14988809; 15940695; 12612583; 8290091
Phenotypes for gene: FLNA were changed from FRONTOMETAPHYSEAL DYSPLASIA 305620; FG SYNDROME TYPE 2 300321; X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION 300048; MELNICK-NEEDLES SYNDROME 309350; Childhood Interstitial Lung Disease; EPILEPTIC ENCEPHALOPATHY; OTOPALATODIGITAL SYNDROME TYPE 1 311300; OTOPALATODIGITAL SYNDROME TYPE 2 304120; TERMINAL OSSEOUS DYSPLASIA 300244 to PERIVENTRICULAR NODULAR HETEROTOPIA 1 300049; FRONTOMETAPHYSEAL DYSPLASIA 305620; FG SYNDROME TYPE 2 300321; X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION 300048; MELNICK-NEEDLES SYNDROME 309350; Childhood Interstitial Lung Disease; EPILEPTIC ENCEPHALOPATHY; OTOPALATODIGITAL SYNDROME TYPE 1 311300; OTOPALATODIGITAL SYNDROME TYPE 2 304120; TERMINAL OSSEOUS DYSPLASIA 300244
Mode of inheritance for gene: FLNA was changed from X linked: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rebecca Foulger: Original DDG2P rating: confirm
Tag mosaicism tag was added to gene: FLNA.
Added phenotypes Childhood Interstitial Lung Disease for gene: FLNA Publications for gene FLNA were changed from 17632775 to 16299064; 20014127; 11532987; 11914408; 8290091; 9883725; 14988809
Added phenotypes FG SYNDROME TYPE 2 300321 for gene: FLNA Publications for gene FLNA were changed from 12612583 to 17632775
Added phenotypes FRONTOMETAPHYSEAL DYSPLASIA 305620 for gene: FLNA Publications for gene FLNA were changed from 12612583; 17431908 to 12612583
Added phenotypes OTOPALATODIGITAL SYNDROME TYPE 2 304120 for gene: FLNA Publications for gene FLNA were changed from 23037936; 8644737 to 12612583; 17431908
Added phenotypes X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION 300048 for gene: FLNA Publications for gene FLNA were changed from 12612583 to 23037936; 8644737
Added phenotypes MELNICK-NEEDLES SYNDROME 309350 for gene: FLNA Publications for gene FLNA were changed from 10982965 to 12612583
Added phenotypes TERMINAL OSSEOUS DYSPLASIA 300244 for gene: FLNA Publications for gene FLNA were changed from 23934111 to 10982965
Added phenotypes EPILEPTIC ENCEPHALOPATHY for gene: FLNA Publications for gene FLNA were changed from 15654694; 15940695; 12612583; 16596676 to 23934111
gene: FLNA was added gene: FLNA was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: FLNA was set to X linked: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: FLNA were set to 15654694; 15940695; 12612583; 16596676 Phenotypes for gene: FLNA were set to OTOPALATODIGITAL SYNDROME TYPE 1 311300