Fetal hydrops

Gene: FOXP3

Green List (high evidence)

FOXP3 (forkhead box P3)
EnsemblGeneIds (GRCh38): ENSG00000049768
EnsemblGeneIds (GRCh37): ENSG00000049768
OMIM: 300292, Gene2Phenotype
FOXP3 is in 15 panels

4 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: FOXP3 added to the panel by expert. Expert review green, plus literature review confirms role of FOXP3 in fetal hydrops. FOXP3 is a confirmed DD gene for IPEX disorder (OMIM:304790).
Created: 15 Dec 2016, 11:58 a.m.
PMID:26387632 (Rae et al., 2015) report a female patient with recurrent miscarriage. The patient’s first pregnancy aged 34yrs resulted in the death of a male fetus at 18 weeks due to hydrops fetalis. Aged 37yrs, a 3rd pregnancy resulted in a male with fatal hydrops fetalis at 20 weeks. A 4th pregnancy aged 39yr resulted in a male fetus with fetal akinesia, progressive hydrops and termination at 18 weeks. The mutation FOXP3 c.1009C>T p.(Arg337Ter) was identified in fetal tissue of the 3rd and 4th miscarriages. Carrier status of p. Arg337Ter, with random X inactivation, was confirmed in the mother.
Created: 15 Dec 2016, 11:55 a.m.
PMID:26395338 (Reichert et al., 2016) describe a family who suffered the loss of two male fetuses as a result of fetal hydrops. Whole Exome Sequencing on fetal remains following the second loss identified a novel nonsense mutation in the FOXP3 gene: c.1009C>T (p.R337X). The authors note that fetal hydrops as part of IPEX Syndrome had been described previously, and FOXP3 is a confirmed DD gene for IPEX syndrome.
Created: 15 Dec 2016, 11:48 a.m.
Comment on mode of inheritance: Mode of inheritance suggested by reviewers and confirmed by OMIM.
Created: 15 Dec 2016, 10:58 a.m.
Comment on list classification: Updated rating from Red to Green based on 3 Green reviews (includes a review from Diana Wellseley who added FOXP3 to the panel as a new gene) and a literature review (PMID:26395338).
Created: 15 Dec 2016, 10:49 a.m.

Liona Poon (The Chinese University of Hong Kong)

Green List (high evidence)

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

Phenotypes
X-linked syndrome of immunodysregulation, polyendocrinopathy, and enteropathy; fetal hydrops

Publications

Tessa Homfray (Consultant Medical Genetics NHS)

Green List (high evidence)

Strong evidence that this is a new gene for Fetal Hydrops
Created: 8 Dec 2016, 3:45 p.m.

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

Phenotypes
Fetal Hydrops, Absent skeletal Muscle, IPEX

Diana Wellesley (nhs)

Green List (high evidence)

Personal experience of 3 foetuses with hydrops in this condition
Created: 22 Nov 2016, 10:05 a.m.
Personal experience and further paper from 3 centres underway. Probably only for severe mutations. Rating high for severe mutations
Created: 14 Nov 2016, 5:14 p.m.

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

Phenotypes
IPEX

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
Phenotypes
  • Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790
  • IPEX
  • X-linked syndrome of immunodysregulation, polyendocrinopathy, and enteropath
  • fetal hydrops
  • Absent skeletal Muscle
OMIM
300292
Clinvar variants
Variants in FOXP3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 Dec 2016, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

21 December 2016. External reviews were assessed, and panel was revised according to expert review, internal discussion and additional curation. Following internal discussion, all genes from the V1.14 'RASopathies' panel were added as green EXCLUDING NF1 and SPRED1- a cautious approach was taken because Fetal hydrops is a fetal panel. All relevant genes from the 'Mucopolysaccharideosis, Gaucher, Fabry' V1.0 panel (lysosomal storage disorders) were also added to the Fetal hydrops panel as green together with genes from the literature where there is a reasonable link between the corresponding lysosomal storage disorder (LSD) and Fetal hydrops. All PEX genes from the V1.2 'Peroxisomal disorders' panel were added as green based on a link between peroxisomal biogenesis disorders and Fetal hydrops.

15 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

15 Dec 2016, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for FOXP3 were set to Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790; IPEX; X-linked syndrome of immunodysregulation, polyendocrinopathy, and enteropath; fetal hydrops; Absent skeletal Muscle

15 Dec 2016, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for FOXP3 were set to Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790; IPEX; X-linked syndrome of immunodysregulation, polyendocrinopathy, and enteropath; fetal hydrops

15 Dec 2016, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for FOXP3 was changed to X-LINKED: hemizygous mutation in males, biallelic mutations in females

15 Dec 2016, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FOXP3 were set to 26387632; 26395338

15 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

15 Dec 2016, Gel status: 0

Approved Gene

Rebecca Foulger (Genomics England curator)

This proposed gene was validated and added to this panel

14 Nov 2016, Gel status: 0

Added New Source

Diana Wellesley (nhs)

FOXP3 was added to Fetal hydropspanel. Sources: Literature,Other

14 Nov 2016, Gel status: 0

Created

Diana Wellesley (nhs)

FOXP3 was created by dgw