Fetal hydrops
Gene: FOXP3Comment 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.
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
Strong evidence that this is a new gene for Fetal HydropsCreated: 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
Personal experience of 3 foetuses with hydrops in this conditionCreated: 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 mutationsCreated: 14 Nov 2016, 5:14 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
IPEX
Publications
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.
This gene has been classified as Green List (High Evidence).
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
Phenotypes for FOXP3 were set to Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790; IPEX; X-linked syndrome of immunodysregulation, polyendocrinopathy, and enteropath; fetal hydrops
Mode of inheritance for FOXP3 was changed to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for FOXP3 were set to 26387632; 26395338
This gene has been classified as Green List (High Evidence).
This proposed gene was validated and added to this panel
FOXP3 was added to Fetal hydropspanel. Sources: Literature,Other
FOXP3 was created by dgw