Neonatal diabetes
Gene: BSCL2
Initial gene list and info collated by Sian Ellard, University of Exeter Medical School, August 2018 on behalf of the GMS Endocrinology specialist test group. Gene Symbol submitted: BSCL2; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Phenotypes: Neonatal diabetes and generalised lipodystrophy.Created: 11 Jan 2019, 4:27 p.m.
Comment when marking as ready: Marked as ready, May 30th 2017.Created: 30 May 2017, 9:51 a.m.
Comment on list classification: Updated rating from Grey to Green after internal clinical discussion. Gene was added (and rated Green) by Sian Ellard. Aligning with green rating of BSCL2 on multiple diabetes PanelApp panels- although diabetes diagnosis is generally later for BSCL2 patients, neonatal cases are reported.Created: 30 May 2017, 9:51 a.m.
Elisa De-Franco (University of Exeter Medical School) reports 1 patient with neonatal diabetes as result of a mutation in BSCL2; the patient had hyperglycemia detected in the first 2 weeks of life and generalised lipodistrophy. Elisa notes that diabetes is usually diagnosed later on in patients with BSCL2 mutations [personal communication, May 24th 2017].
Created: 25 May 2017, 9:47 a.m.
PMID:11479539 (Magre et al., 2001) identify 11 families where Congenital generalized lipodystrophy maps to BSCL2 (neonatal diagnosis is not specifically mentioned). Congenital generalized lipodystrophy/Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance.
Created: 25 May 2017, 9:42 a.m.
Phenotypes for gene: BSCL2 were changed from Congenital generalised lipodystrophy, severe insulin resistance and diabetes; Neonatal diabetes and generalised lipodystrophy; Lipodystrophy, congenital generalized, type 2, 269700 to Congenital generalised lipodystrophy, severe insulin resistance and diabetes; Neonatal diabetes and generalised lipodystrophy; Lipodystrophy, congenital generalized, type 2, OMIM:269700
Phenotypes for gene: BSCL2 were changed from Congenital generalised lipodystrophy, severe insulin resistance and diabetes to Congenital generalised lipodystrophy, severe insulin resistance and diabetes; Neonatal diabetes and generalised lipodystrophy; Lipodystrophy, congenital generalized, type 2, 269700
Source NHS GMS was added to BSCL2. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted panel to Version 1: 31st May 2017. This panel is largely aligned with the Exeter Molecular Genetics Laboratory neonatal diabetes screen. Note that 8 genes feature on the Exeter 8-gene panel for patients with 'neonatal diabetes and autoimmune disease' (FOXP3, IL2RA, ITCH, LRBA, SIRT1, STAT1, STAT3 and STAT5). ITCH, SIRT1, STAT1 and STAT5A/B do not feature on this panel following correspondance with Elisa De-Franco (University of Exeter Medical School) that, at the time of curation, none of the patients with mutations in ITCH, SIRT1, STAT1 and STAT5b had diabetes diagnosed in the neonatal period, and therefore there is currently insufficient evidence to include these genes in this neonatal diabetes panel.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Phenotypes for BSCL2 were set to Congenital generalised lipodystrophy, severe insulin resistance and diabetes
Publications for BSCL2 were set to 11479539
BSCL2 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Expert Review