Osteogenesis imperfecta
Gene: B4GALT7
Following discussion with Dr Balasubramanian - rate green. Can have osteopenia, advanced bone age. PMID: 26940150 Mutations in this gene have been associated with the rare progeroid form of Ehlers Danlos syndrome and in addition more recently found to underlie Larsen of Reunion Island syndrome. Nine individuals have been reported with a diagnosis of the progeroid form of Ehlers Danlos syndrome, four of whom have had molecular characterization showing homozygous or compound heterozygous mutations in B4GALT7. We report two newly described patients with compound heterozygous mutations in B4GALT7, and show that the six individuals with confirmed mutations do not have the progeroid features described in the original five patients with a clinical diagnosis of the progeroid form of Ehlers Danlos syndrome. Results in a clinically recognizable syndrome comprising short stature, joint hypermobility, radioulnar synostosis, and severe hypermetropia. This group of syndromic patients are on a phenotypic spectrum with individuals who have Larsen of Reunion Island syndrome, although the key features of osteopenia, fractures and hypermetropia have not been reported in patients from Reunion Island.Created: 3 Apr 2019, 4:14 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Ehlers-Danlos syndrome, spondylodysplastic type, 1 130070
Publications
Comment on list classification: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.Created: 11 Jun 2019, 3:19 p.m.
This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.Created: 11 Jun 2019, 1:17 p.m.
Associated with Ehlers-Danlos syndrome, spondylodysplastic type, 1 (#130070) in OMIM.
PMID: 26940150 - Salter et al 2016 - two unrelated patients with compound heterozygous mutations in B4GALT7. Both showed osteopenia (one with fractures, other patient had mild osteopenia). They review the phenotypes reported in previous cases (Table 1): 1 case with osteopenia reported in Faiyaz‐Ul‐Haque et al. [2004] , 1 case reported in Kresse et al. [1987] (with possible rib fracture).
Summary: 3 cases of patients with homozygous or compound heterozygous variants in B4GALT7 and osteopenia, 2 with fractures.Created: 11 Jun 2019, 12:55 p.m.
This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: B4GALT7; Suggested initial gene rating: greenCreated: 3 Apr 2019, 4:08 p.m.
Comment when marking as ready: Keep as red as disagreement between expert reviewers are query association with OICreated: 10 May 2016, 3:13 p.m.
Variants in this gene cause progeroid EDS. Why should this be considered to be an OI gene?Created: 8 Dec 2015, noon
Progeroid EDSCreated: 27 Nov 2015, 3:03 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
There is insufficient evidence to support a causal role of this gene in this particular diseaseCreated: 6 Oct 2015, 11:35 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
EDS progeroid
Publications
Gene: b4galt7 has been classified as Green List (High Evidence).
Mode of inheritance for gene: B4GALT7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALT7 were set to 15211654; 26940150
Publications for gene: B4GALT7 were set to
Phenotypes for gene: B4GALT7 were changed from Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias to Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; Ehlers-Danlos syndrome, spondylodysplastic type, 1 130070
Source NHS GMS was added to B4GALT7.
This gene has been classified as Red List (Low Evidence).
B4GALT7 was added to Osteogenesis Imperfecta panel. Sources: Emory Genetics Laboratory