Hereditary haemorrhagic telangiectasia
Gene: SMAD4EnsemblGeneIds (GRCh38): ENSG00000141646
EnsemblGeneIds (GRCh37): ENSG00000141646
OMIM: 600993, Gene2Phenotype
SMAD4 is in 23 panels
4 reviews
Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
On CGGL Royal Brompton HHT diagnostic panel. Extensive literature evidence. causes combined syndrome of HHT and juvenile polyposis syndromeCreated: 22 Sep 2019, 8:09 p.m. | Last Modified: 22 Sep 2019, 8:09 p.m.
Panel Version: 1.51
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
OMIM: 175050 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
Publications
Variants in this GENE are reported as part of current diagnostic practice
Louise Daugherty (Genomics England Curator)
Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted SMAD4; Suggested initial gene rating: Green; Evidence for inclusion: OMIM Juvenile polyposis & HHT gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none givenCreated: 6 Dec 2018, 12:36 p.m.
Sarah Leigh (Genomics England Curator)
Comment when marking as ready: Associated with phenotype in OMIM and as a "Plausible disease-causing mutations within, affecting or encompassing the coding region of a single gene identified in multiple (>3) unrelated cases/families with both a developmental disorder and an incidental (nondevelopmental)" disorder Developmental Disorder Gene / G2P. At least 7 variants reported.Created: 12 Dec 2016, 11:48 a.m.
Comment on phenotypes: Also associated with Polyposis, juvenile intestinal, 174900; Myhre syndrome, 139210; Pancreatic cancer, somatic 260350.
Additional HPO terms added by Claire Shovlin: Epistaxis (HP:0000421); Nasal mucosa telangiectasia (HP:0000434); Lip telangiectasia (HP:0000214); Tongue telangiectasia (HP:0000227); Palate telangiectasia (HP:0002707) Finger pad telangiectasia (pulp not nail side); Gastrointestinal telangiectasia (HP:0002604); Arteriovenous malformation (HP:0100026); Cerebral arteriovenous malformation (HP:0002408); Pulmonary arteriovenous malformation (HP:0006548); Hepatic arteriovenous malformation (HP:0006574)Spinal arteriovenous malformation (HP:0002390). Additional phenotypes secondary to these diagnostic criteria. Juvenile polyposis HP: 0012198; Dilatation ascending aorta HP: 005111Created: 12 Dec 2016, 11:44 a.m.
Claire Shovlin (Imperial College London)
OMIM #175050 JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME; JPHT.
Created: 13 Nov 2016, 10 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epistaxis (HP:0000421); Nasal mucosa telangiectasia (HP:0000434); Lip telangiectasia (HP:0000214); Tongue telangiectasia (HP:0000227); Palate telangiectasia (HP:0002707) Finger pad telangiectasia (pulp not nail side); Gastrointestinal telangiectasia (HP:0002604); Arteriovenous malformation (HP:0100026); Cerebral arteriovenous malformation (HP:0002408); Pulmonary arteriovenous malformation (HP:0006548); Hepatic arteriovenous malformation (HP:0006574)Spinal arteriovenous malformation (HP:0002390). Additional phenotypes secondary to these diagnostic criteria. Juvenile polyposis HP: 0012198; Dilatation ascending aorta HP: 005111
Publications
- PMID 15031030
Variants in this GENE are reported as part of current diagnostic practice
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- NHS GMS
- Eligibility statement prior genetic testing
- Expert Review Green
- Radboud University Medical Center, Nijmegen
- Emory Genetics Laboratory
- UKGTN
- UKGTN
- Emory Genetics Laboratory
- Radboud University Medical Center, Nijmegen
- Phenotypes
-
- Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
- OMIM
- 600993
- Clinvar variants
- Variants in SMAD4
- Penetrance
- Complete
- Publications
- Panels with this gene
-
- Vascular skin disorders
- Thoracic aortic aneurysm or dissection (GMS)
- Pulmonary arterial hypertension
- Bleeding and platelet disorders
- DDG2P
- Clefting
- Cerebral vascular malformations
- Colorectal cancer pertinent cancer susceptibility
- Adult solid tumours for rare disease
- GI tract tumours
- Childhood solid tumours
- Adult solid tumours cancer susceptibility
- Thoracic aortic aneurysm or dissection
- Structural eye disease
- Arthrogryposis
- Inherited bleeding disorders
- Ehlers Danlos syndrome with a likely monogenic cause
- Skeletal dysplasia
- Inherited polyposis and early onset colorectal cancer - germline testing
- Fetal anomalies
- Hereditary haemorrhagic telangiectasia
- Childhood solid tumours cancer susceptibility
- Intellectual disability
History Filter Activity
Added New Source, Status Update
Louise Daugherty (Genomics England Curator)Source NHS GMS was added to SMAD4. Rating Changed from Green List (high evidence) to Green List (high evidence)
Upload gene information
Ellen McDonagh (Genomics England Curator)SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Eligibility statement prior genetic testing
panel promoted to version 1
Sarah Leigh (Genomics England Curator)Promoted to V1 (12th December 2016)
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Set Phenotypes
Sarah Leigh (Genomics England Curator)Phenotypes for SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
Set Phenotypes
Sarah Leigh (Genomics England Curator)Phenotypes for SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050; ; Hereditary Hemorrhagic Telangiectasia; Hereditary hemorrhagic telangiectasia (HHT); Juvenile Polyposis/Hereditary Hemorrhagic Telangiectasia Syndrome
Set publications
Sarah Leigh (Genomics England Curator)Publications for SMAD4 were set to 15031030
Set Mode of Inheritance
Sarah Leigh (Genomics England Curator)Mode of inheritance for SMAD4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added New Source
Ellen McDonagh (Genomics England Curator)SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Source: Illumina TruGenome Clinical Sequencing Services
Added New Source
Ellen McDonagh (Genomics England Curator)SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Source: UKGTN
Added New Source
Ellen McDonagh (Genomics England Curator)SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Source: Emory Genetics Laboratory
Set Mode of Inheritance, Added New Source
Ellen McDonagh (Genomics England Curator)SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Source: Illumina TruGenome Clinical Sequencing Services Model of inheritance for gene SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added New Source
Ellen McDonagh (Genomics England Curator)SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Source: Radboud University Medical Center, Nijmegen
Created
Ellen McDonagh (Genomics England Curator)SMAD4 was created by ellenmcdonagh
Added New Source
Ellen McDonagh (Genomics England Curator)SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Eligibility statement prior genetic testing