Endocrine Abstracts

Marshall-Smith syndrome (MSS) is a congenital disorder characterised by developmental delay, failure to thrive and skeletal abnormalities such as accelerated osseous development, osteopenia, bullet-shaped middle phalanges and kyphoscoliosis. MSS is caused by truncating or frameshift mutations of the nuclear factor I/X (NFIX) gene, which encodes a ubiquitously expressed transcription factor that regulates expression of viral and cellular genes, i...

Marshall-Smith syndrome (MSS) is a congenital disorder characterised by developmental delay, failure to thrive and skeletal abnormalities such as accelerated osseous development, osteopenia, bullet-shaped middle phalanges and kyphoscoliosis. MSS is caused by truncating or frameshift mutations of the nuclear factor I/X (NFIX) gene, which encodes a ubiquitously expressed transcription factor that regulates expression of viral and cellular genes, i...

Marshall-Smith syndrome (MSS) is a congenital disorder affecting skeletal and neural development, due to mutations in the nuclear factor I/X (NFIX) gene. NFIX encodes a ubiquitously expressed transcription factor that regulates the expression of viral and cellular genes. To identify novel genes that are misregulated by NFIX mutations, RNA sequencing and proteomics analyses were performed on mouse embryonic fibroblast (MEF) cells derived from a repres...

Marshall-Smith syndrome (MSS) is a congenital disorder affecting skeletal and neural development due to mutations in the nuclear factor I/X (NFIX) gene. Of these mutations, 61% are small insertions/deletions, 12% are splice site mutations and 27% are large exonic deletions clustered in exons 6–10 of the NFIX gene. In order to derive a MSS mouse model, the N-ethyl-N-nitrosourea (ENU) mutagenesis DNA archive was screened ...

Heterozygous germline gain-of-function mutations of the extracellular calcium-sensing receptor (CaSR), a G-protein coupled receptor (GPCR), result in autosomal dominant hypocalcaemia type 1 (ADH1), which may cause symptomatic hypocalcaemia with low circulating parathyroid hormone (PTH) concentrations and hypercalciuria. Negative allosteric CaSR modulators, known as calcilytics, rectify the gain-of-function caused by CaSR mutations and are a potential targeted therapy for ADH1....

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the occurrence of parathyroid, pancreatic and pituitary tumours, and is due to mutations of the MEN1 gene, which encodes menin. We have investigated identical twins with MEN1, one of whom developed primary hyperparathyroidism (PHPT) and a prolactinoma that caused pubertal arrest, and the other had PHPT only. DNA sequence analysis of the MEN1 coding region had not ide...

G-protein subunit α-11 (Gα11), which is encoded by GNA11, plays a major role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion, and germline loss-of-function mutations cause familial hypocalciuric hypercalcaemia type 2 (FHH2). Since Gα11 is ubiquitously expressed, we investigated whether FHH2 is associated with additional non-calcitropic phenotypes by analysing mice harbouring a homozygous germline deletion o...

Familial hypocalciuric hypercalcaemia type 1 (FHH1) is mainly caused by loss-of-function missense mutations of the extracellular calcium-sensing receptor (CaSR), which is a parathyroid- and kidney-expressed G-protein coupled receptor that plays a pivotal role in mineral metabolism. Here, we report the unusual occurrence of a novel heterozygous in-frame CASR exon 4 deletion, c.(492+1_493-1)_(1377+1_1378-1)del, in a family with FHH1. This mutation is predicted...

Marshall-Smith syndrome (MSS) is a congenital disorder characterised by developmental delay, short stature, respiratory difficulties, distinctive facial features, skeletal abnormalities (such as kyphoscoliosis, dysostosis and osteopenia) and delayed neural development, and is due to heterozygous mutations that are clustered in exons 6–10 of the transcription factor nuclear factor I/X (NFIX) gene. These frameshift and splice-site NFIX variants result in t...