Intellectual disability
Gene: FBXO11

FBXO11 (F-box protein 11)
EnsemblGeneIds (GRCh38): ENSG00000138081
EnsemblGeneIds (GRCh37): ENSG00000138081
OMIM: 607871, Gene2Phenotype
FBXO11 is in 6 panels

2 reviews

Helen Brittain (Genomics England Curator)

Comment on list classification: Appropriate phenotype, sufficient number of cases.
Created: 5 Oct 2018, 8:38 a.m.

Comment when marking as ready: Appropriate phenotype and sufficient cases
Created: 5 Oct 2018, 8:19 a.m.

Created: 5 Oct 2018, 8:19 a.m.

Panel version: 2.506

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID 30057029 is a collaborative study (including individuals from the DDD study) on 20 individuals with de novo FBXO11 variants including 8 missense variants, 10 likely gene desrupting (or LGD incl. nonsense, splice site, frameshift), 1 partial gene deletion and 1 whole gene deletion. Developmental delay was universal feature and most individuals presented with ID (profound in those with missense, severe in those with LGD variants, 2 individuals with normal IQ but difficulties in specific domains). 85% presented with behavioral anomalies incl.autistic features. 5 individuals (25%) were reported to have seizures. Cleft lip/palate/bifid uvula was a feature in 3 subjects (15%). Variable occipitofrontal circumference and skeletal features. The authors suggest loss-of-function/haploisufficiency as a plausible mechanism although gain-of-function and dominant negative effects were possible, particularly for missense variants. //

PMID 29796876 reports on 2 individuals, one with de novo insertion affecting a splice donor site, the other with a de novo frameshift variant, both with developmental delay, intellectual disability and behavioral problems. Microcephaly and cleft lip/alveolus were features in one individual. Seizures were not noted. //

De novo variants in individuals with intellectual disability had previously been reported without clinical details in PMID 27620904 (1 individual with the same frameshift variant as in PMID 29796876) as well as in a meta-analysis of 2104 trios with intellectual disability (PMID 27479843 - 2 individuals). //

As pointed out in 30057029, a study of 152 consanguineous families with neurodevelopmental disorders (PMID 28097321) had previously identified one individual homozygous for a missense FBXO11 variant (individual MR136). This subject was reported to have hypotonia, severe intellectual disability and EEG abnormalities.

As a result other modes of inheritance (eg. BOTH monoallelic and biallelic, with biallelic causing a more severe phenotype) cannot be ruled out - and may be considered.
Created: 15 Aug 2018, 7:32 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures

Publications

Created: 15 Aug 2018, 7:32 p.m.

Panel version: 2.393

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green

Phenotypes

Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities 618089

OMIM

607871

Clinvar variants

Variants in FBXO11

Penetrance

unknown

Publications

Panels with this gene

History Filter Activity

5 Oct 2018, Gel status: 3

Entity classified by Genomics England curator

Helen Brittain (Genomics England Curator)

Gene: fbxo11 has been classified as Green List (High Evidence).

5 Oct 2018, Gel status: 2

Entity classified by Genomics England curator

Helen Brittain (Genomics England Curator)

Gene: fbxo11 has been classified as Amber List (Moderate Evidence).

25 Sep 2018, Gel status: 2