Gastrointestinal neuromuscular disorders

Gene: FLNA

Green List (high evidence)

FLNA (filamin A)
EnsemblGeneIds (GRCh38): ENSG00000196924
EnsemblGeneIds (GRCh37): ENSG00000196924
OMIM: 300017, Gene2Phenotype
FLNA is in 24 panels

2 reviews

Ellen McDonagh (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Gene rated green and diagnostic by reviewer. 2 family reports and unrelated singleton in OMIM - these cases all include a 2-bp deletion in exon 2 (6_17delTC rs398122521 and rs80338840 65-66delAC have been reported). Further cases found in literature search PMID: 26059841 - a 4bp deletion in exon 40 identified in two siblings who had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO, and PMID: 20871226. PMID: 18854860 - duplications of several genes in the region. Overall, more than 3 family reports.
Created: 19 Oct 2016, 10:12 a.m.

Neil shah (GOSH)

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Intestinal pseudoobstruction, neuronal 300048
  • Congenital short bowel syndrome 300048
OMIM
300017
Clinvar variants
Variants in FLNA
Penetrance
Complete
Publications
  • 17357080
  • 23037936
  • 26059841 - the two siblings who had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. A 4-bp deletion in exon 40 was reported, and functional studies revealed that the variant induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. "Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses."
  • 20871226
  • 18854860
Panels with this gene

History Filter Activity

26 Oct 2016, Gel status: 4

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

26th October 2016: panel revised after expert review and further curation of the analysis, with then internal clinical review. Ready for promotion to version 1.

19 Oct 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

19 Oct 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for FLNA were set to 17357080; 23037936; 26059841 - the two siblings who had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. A 4-bp deletion in exon 40 was reported, and functional studies revealed that the variant induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. "Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses."; 20871226; 18854860

19 Oct 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for FLNA were set to 17357080; 23037936; 26059841 - the two siblings who had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. A 4-bp deletion in exon 40 was reported, and functional studies revealed that the variant induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. "Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses.";20871226

19 Oct 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for FLNA were set to 17357080; 23037936; 26059841 - the two siblings who had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. A 4-bp deletion in exon 40 was reported, and functional studies revealed that the variant induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. "Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses."

19 Oct 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for FLNA were set to 17357080; 23037936;PMID: 26059841 - the two siblings who had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. A 4-bp deletion in exon 40 was reported, and functional studies revealed that the variant induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. "Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses."

19 Oct 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

19 Oct 2016, Gel status: 2

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for FLNA were set to Intestinal pseudoobstruction, neuronal 300048; Congenital short bowel syndrome 300048

19 Oct 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for FLNA were set to 17357080;23037936

19 Oct 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for FLNA were set to 17357080

31 Aug 2016, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

FLNA was added to Neonatal and familial gastrointestinal neuromuscular disorderspanel. Source: Radboud University Medical Center, Nijmegen

31 Aug 2016, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

FLNA was added to Neonatal and familial gastrointestinal neuromuscular disorderspanel. Sources: UKGTN

31 Aug 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

FLNA was created by sleigh