Paediatric pseudo-obstruction syndrome
Gene: FLNA
The rating of this gene has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 7:44 a.m. | Last Modified: 1 Feb 2023, 7:44 a.m.
Panel Version: 0.216
Comment on classification of this gene: The rating for this gene should be GREEN as this gene has been implicated in intestinal pseudo-obstruction, as identified from five unrelated families.
Four patients from family 1 reported with intestinal pseudo-obstruction in PMID:20871226 had diffuse abnormal layering of small intestinal smooth muscle (DAL). At least five males were affected in this family and they were all maternally-related. Both the mother and sister of patient 1 have normal intestinal motility and cranial magnetic resonance imaging, but the sister had a PDA and bifid uvula. Patient 5 from a second family was also reported with variant in FLNA gene (c.7021C>T; p.Gln2341Ter) and the parents also gave birth to a healthy female. Bot these cases suggest biallelic mode of inheritance in females.
2-bp deletion in exon 2 of the FLNA gene was found in the male proband and his second cousin and the variant was present in heterozygous state in the carrier females of the family (PMID:17357080). Similarly, a 4-bp deletion in exon 40 was identified in PMID:26059841, which results in translation of a mutant FLNA missing an internal region of 41 amino acids.
In another family, three males and four females were identified with a novel no-stop FLNA mutation (c.7941_7942delCT, p.(*2648Serext*100)). This variant causes classical X-linked periventricular nodular heterotopia (XL-PNH) in females and an unusual multi-organ phenotype in males (PMID:23873601).
This gene is associated with relevant phenotypes in both OMIM and Gene2Phenotype.Created: 20 Dec 2022, 10:22 p.m. | Last Modified: 20 Dec 2022, 10:43 p.m.
Panel Version: 0.36
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Congenital short bowel syndrome, OMIM:300048; Intestinal pseudoobstruction, neuronal, OMIM:300048
Publications
Review submitted on behalf of Dr. Anna Rybak and Dr. Osvaldo Borreli, Great Ormond Street Hospital for Children NHS Foundation Trust. Gene group: Myopathic PIPO/MMIHS. Protein function: Filamin A, Encodes large cytoskeletal proteins.Created: 20 Dec 2022, 3:32 p.m. | Last Modified: 20 Dec 2022, 3:32 p.m.
Panel Version: 0.2
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
Cytoskeletal abnormalities and potentially disrupts enteric-neuron structure and function. Seizures and progressive abdominal distension and obstruction
Publications
Publications for gene: FLNA were set to 17357080; 20871226; 23873601; 26059841; 31848803; 33729000
Phenotypes for gene: FLNA were changed from to Congenital short bowel syndrome, OMIM:300048; Intestinal pseudoobstruction, neuronal, OMIM:300048
Publications for gene: FLNA were set to
Mode of inheritance for gene: FLNA was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Gene: flna has been classified as Green List (High Evidence).
gene: FLNA was added gene: FLNA was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list Mode of inheritance for gene: FLNA was set to