Genetics of Growth Hormone Deficiency: Insights from a Cohort of 203 Patients.

Context: Growth Hormone (GH) deficiency is a rare disorder characterized by severe short stature, which can result from genetic mutations affecting hypothalamic-pituitary development and function.

Objective: To determine the genetic basis of GH deficiency in a Portuguese cohort.

Design, Setting, Patients: Multicentre cohort of 203 GH-deficient patients (78 with Isolated GH Deficiency (IGHD) and 125 with Combined Pituitary Hormone Deficiency (CPHD)) were analysed.

Germline genetic variants in young-onset sporadic pituitary macroadenomas: A multigene panel analysis.

Mutations in several genes have been associated with familial forms of pituitary adenomas. Sporadic pituitary adenomas (i.e.

Kallmann Syndrome: Functional Analysis of a Missense Variant Shows Aberrant RNA Splicing.

Kallmann syndrome is a rare disorder characterized by hypogonadotropic hypogonadism and an impaired sense of smell (anosmia or hyposmia) caused by congenital defects in the development of the gonadotropin-releasing hormone (GnRH) and olfactory neurons. Mutations in several genes have been associated with Kallmann syndrome. However, genetic testing of this disorder often reveals variants of uncertain significance (VUS) that remain uninterpreted without experimental validation.

Hypoparathyroidism, deafness and renal dysplasia syndrome caused by a splice site mutation leading to the activation of a cryptic splice site.

The HDR syndrome is a rare autosomal dominant disorder characterised by Hypoparathyroidism, Deafness, and Renal dysplasia, and is caused by inactivating heterozygous germline mutations in the gene. We report an 11-year-old girl with HDR syndrome caused by a heterozygous mutation located at the splice acceptor site of exon 5 of the gene (NM_001002295.2: c.

A Common Variant in the Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study.

The majority of pituitary adenomas occur in a sporadic context, and in the absence of known genetic predisposition. Three common variants at the (rs2359536), (rs10763170) and (rs17083838) loci were previously associated with sporadic pituitary adenomas in the Han Chinese population, but these findings have not yet been replicated in any other population. The aim of this case-control study was to assess if these variants are associated with susceptibility to sporadic pituitary adenomas in the Portuguese population.

Disorder of Sex Development Due to 17-Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency: A Case Report and Review of 70 Different Mutations Reported in 239 Patients.

The 17-beta-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) enzyme converts androstenedione to testosterone and is encoded by the HSD17B3 gene. Homozygous or compound heterozygous HSD17B3 mutations block the synthesis of testosterone in the fetal testis, resulting in a Disorder of Sex Development (DSD). We describe a child raised as a female in whom the discovery of testes in the inguinal canals led to a genetic study by whole exome sequencing (WES) and to the identification of a compound heterozygous mutation of the HSD17B3 gene (c.

A Novel Missense Mutation in a Portuguese Family with Congenital Hypogonadotropic Hypogonadism.

Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive endocrine disorder characterized by complete or partial failure of pubertal development and infertility due to deficiency of the gonadotropin-releasing hormone (GnRH). CHH has a significant clinical heterogeneity and can be caused by mutations in over 30 genes. The aim of this study was to investigate the genetic defect in two siblings with CHH.

Maturity-Onset Diabetes of the Young (MODY) in Portugal: Novel , and Mutations.

Maturity-onset diabetes of the young (MODY) is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. The most frequent subtypes are due to mutations of the (MODY 2), (MODY 3), and (MODY 1) genes. We undertook the first multicenter genetic study of MODY in the Portuguese population.

Association of Vitamin D Pathway Genetic Variation and Thyroid Cancer.

Vitamin D is mostly known for its role in bone and calcium metabolism. However, studies have suggested that it also has inhibitory effects on tumor development and progression. Genetic variants close to genes that encode crucial enzymes for the synthesis ( rs12785878), metabolism ( rs2060793) and degradation ( rs6013897) of vitamin D have been associated with serum levels of vitamin D.

biallelic and digenic mutations in patients with normosmic congenital hypogonadotropic hypogonadism.

Objective: Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disorder characterised by lack of pubertal development and infertility, due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH) and, unlike Kallmann syndrome, is associated with a normal sense of smell. Mutations in the gene cause autosomal recessive nCHH. The aim of this study was to determine the prevalence of mutations in a group of 40 patients with nCHH.