Endocrine Abstracts

3M syndrome is characterised by severe intra-uterine and post-natal growth failure. Patients have a characteristic triangular facial appearance and disproportionate short stature with tall vertebral bodies and over-tubulation of long bones. The condition bears some resemblance to the Russell Silver syndrome, but is transmitted as an autosomal recessive trait. It has been proposed that heterozygous carriers demonstrate mild phenotypic manifestations of the condition.<p clas...

Expression of the ACTH receptor (MC2R), a 7 transmembrane GPCR, has been difficult to achieve in cell lines that are not of adrenal origin. Heterologous expression of this gene in many cell lines (CHO, Hela, H295R, HEK293) produces a protein that is trapped in the ER, suggesting that an accessory factor(s) might be necessary to traffic MC2R through the cell. We recently identified such an accessory factor, MRAP that rescues MC2R expression in some, but not all, cell lines. Mut...

Enlarged vestibular aqueduct (EVA) is the most common malformation of inner ear associated with sensorineural hearing loss. It can either be found in nonsyndromic or in syndromic forms of hearing loss, such as Pendred syndrome (PS). In PS, sensorineural deafness is associated with thyroid abnormalities: goitre and iodine organification defect detected with perchlorate discharge test. Mutations in SLC26A4 (PDS) gene cause PS and can also be found in a proportion of patients pre...

The regulation of aldosterone secretion is altered in essential hypertension: the phenotype of relative aldosterone excess is present in up to 15% of subjects. The gene encoding aldosterone synthase (CYP11B2) offers an obvious candidate to account for this and a polymorphism in its 5′ untranslated region (UTR; −344C/T) is associated with increased frequency of hypertension and higher aldosterone levels. However, this variation is more closely associated with...

CNC is an autosomal dominant multiple neoplasia syndrome, responsible mainly for cardiac myxomas, pigmented skin lesions and endocrine tumors (acromegaly, thyroid and testicular neoplasms and primary pigmented nodular adrenocortical disease: PPNAD). The PRKAR1A gene was previously found to be mutated in about 41% of CNC kindreds. Most mutations lead to nonsens mediated mRNA decay and preclude expression of the mutant protein. 102 patients (64 with PPNAD and 38 with CNC)...

Paraganglioma and pheochromocytomas are described as sporadic and hereditary conditions. Hereditary are the lesions in the tumor syndromes Multiple endocrine neoplasia type 2 (MEN 2), Von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), and the paraganglioma syndromes type 1 type 3 and type 4 (PGL1, PGL3, PGL4). The susceptibility genes are for PGL1 SDHD, PGL3 SDHC, and for PGL4 SDHB. In contrast to PLG1 and PGL4 in which numerous carriers have...

Premature ovarian failure (POF) is a common cause of female infertility affecting about 1–2% of women under the age of 40. This heterogeneous disorder is characterized by primary or secondary amenorrhea and elevated gonadotropin values. Several defects can cause POF, including autoimmunity, X chromosome abnormalities and gene mutations, but its pathogenesis is still unknown in the vast majority of women with normal karyotype. We recently described two sisters affected wit...

Progressive osseous heteroplasia (POH, MIM 166350) is a rare autosomal dominant disorder characterised by extensive dermal ossification during childhood, followed by widespread heterotopic ossification of skeletal muscle and deep connective tissue. Recently, genetic basis was found to be common with Albright’s hereditary osteodystrophy (AHO) (Shore et al., 2002): paternally inherited inactivating mutations of the GNAS1 gene were found. GNAS1 is the ge...