Endocrine Abstracts

Sphingosine-1-phosphate lyase 1 insufficiency syndrome (SPLIS) is a multisystemic syndrome in which primary adrenal insufficiency (PAI) and steroid resistant nephrotic syndrome predominate, secondary to loss-of-function mutations in SGPL1 (sphingosine-1-phosphate lyase). SGPL1 carries out the irreversible breakdown of sphingosine-1-phosphate, a bioactive sphingolipid intermediate, with implicated roles in various cellular processes. Wider endocrinopathy including gonadal insuf...

Background: A diagnosis Silver–Russell Syndrome (SRS) is important for early institution of appropriate management, access to therapy and reduces the burden of diagnostic uncertainty. SRS is molecularly heterogeneous and 11p15 LOM/upd(7)mat account for ~60% cases. Monogenic causes include variants in HMGA2, CDKN1C, IGF-2, PLAG1 and contribute to 5% cases. Clinical SRS diagnosis requires the fulfilment of ≥4/6 Netchine–Harbison Clinical Scoring ...

Background: Primary adrenal insufficiency (PAI) can be associated with significant morbidity in children of all ages, the most common cause being Congenital Adrenal Hyperplasia (CAH). Several other rare inherited causes of PAI have been identified over the years which lack diagnostic phenotypic or biochemical signs, leaving genetic testing as the only approach to make a definitive diagnosis. Our cohort involves >440 patients who presented with features of PAI – hypogl...

Objectives: Noonan Syndrome (NS) is an autosomal dominant multi-system disorder characterised by short stature (SS), distinctive facial features and cardiovascular abnormalities. Mutations in multiple genes regulating the RAS-MAPK pathway have been identified in NS including 5 recently described novel LZTR1 variants. We identified 2 novel LZTR1 variants in patients with features of growth hormone insensitivity and NS. The molecular function of LZTR1 ...

Objectives: The homozygous GHR pseudoexon (6Ψ) mutation leads to aberrant splicing of the GHR gene with clinical and biochemical heterogeneity. We investigated whether the phenotypic variability could be explained by transcript heterogeneity i.e. ratio of abnormal (6Ψ GHR) to normal (WT GHR) transcripts and/or the presence of concurrent defects in other short stature (SS) genes.Methods: 6 Ψ GHR ...