Fetal anomalies
Gene: BGN
PMID: 27236923 (2016) performed exome sequencing of two previously reported families with X-linked spondyloepimetaphyseal dysplasia. They found two monoallelic missense variants in BGN which segregated with the phenotype in multiple affected male family members. One of the variants was also identified in an additional simplex male individual with a similar phenotype. PMID: 27632686 (2017) reported 3 unrelated male individuals with missense variants, one predicted to affect splicing, and two unrelated males with deletions encompassing BGN. The primary phenotype was aortic aneurysm/dissection. The skeletal phenotype showed some similarities with X-linked spondyloepimetaphyseal dysplasia although some affected individuals had normal or tall stature. The earliest age of onset was age 1 for aortic aneurysm.Created: 7 Jan 2019, 10:17 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Spondyloepimetaphyseal dysplasia, X-linked; Meester-Loeys syndrome
Publications
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Originally rated Amber based on DDG2P Disease confidence of 'both DD and IF' for at least one disorder. Outcome of review: Confirmed that phenotype is fetally-relevant: include on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: Review of BGN as Amber by Anna was before group review of the panel began. Following group review, it was decided that BGN should be included for the skeletal phenotype (Spondyloepimetaphyseal dysplasia) with X-linked RECESSIVE inheritance.Created: 29 Apr 2019, 12:28 p.m.
Removed watchlist tag following clinical review by Anna de Burca.Created: 7 Jan 2019, 11:19 a.m.
Comment on list classification: Originally assigned an Amber rating because of different PAGE/DDG2P ratings for different disorders. Kept rating as Amber based on Anna's review: sufficient evidence for aortic aneurysm.causation but phenotype presents later.Created: 7 Jan 2019, 11:18 a.m.
Comment on mode of inheritance: MOI listed in OMIM as XL for Meester-Loeys syndrome, and XLR for Spondyloepimetaphyseal dysplasia, X-linked.Created: 7 Jan 2019, 11:14 a.m.
'watchlist' tag added to highlight different DD-G2P ratings for this gene.Created: 8 Nov 2018, 9:02 p.m.
In the original PAGE file: rated as Probable for X-Linked Spondyloepimetaphyseal Dysplasia, and rated as Both DD and IF for Severe syndromic form of thoracic aortic aneurysm & dissection. In the original PAGE file, MOP listed as LOF for Severe syndromic form of thoracic aortic aneurysm & dissection, and listed as All missense/in frame for X-Linked Spondyloepimetaphyseal Dysplasia. Mode of inheritance for both disorders in PAGE list: Hemizygous.Created: 8 Nov 2018, 4:46 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Source Expert Review Green was added to BGN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag watchlist was removed from gene: BGN.
Gene: bgn has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: BGN was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: BGN were changed from Severe syndromic form of thoracic aortic aneurysm & dissection; X-Linked Spondyloepimetaphyseal Dysplasia to Severe syndromic form of thoracic aortic aneurysm & dissection; X-Linked Spondyloepimetaphyseal Dysplasia; Meester-Loeys syndrome, 300989; Spondyloepimetaphyseal dysplasia, X-linked, 300106
Publications for gene: BGN were set to
Tag watchlist tag was added to gene: BGN.
Added phenotypes Severe syndromic form of thoracic aortic aneurysm & dissection for gene: BGN
gene: BGN was added gene: BGN was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: BGN was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: BGN were set to X-Linked Spondyloepimetaphyseal Dysplasia