Analysis of the GCM2 gene in isolated hypoparathyroidism: a molecular and biochemical study.

Context: Hypoparathyroidism is characterized by hypocalcemia, hyperphosphatemia, and absent or markedly reduced serum levels of intact PTH. The transcription factor GCM2 is critical for the development of parathyroid glands in mice and humans.

Objective: We sought to determine the prevalence of GCM2 gene mutations in patients with familial or sporadic forms of isolated hypoparathyroidism (IH).

A novel mutation L260P of the steroidogenic acute regulatory protein gene in three unrelated patients of Swiss ancestry with congenital lipoid adrenal hyperplasia.

Context: Lipoid congenital adrenal hyperplasia (CAH) is the most severe form of CAH leading to impaired production of all adrenal and gonadal steroids. Mutations in the gene encoding steroidogenic acute regulatory protein (StAR) cause lipoid CAH.

Objective: We investigated three unrelated patients of Swiss ancestry who all carried novel mutations in the StAR gene.

Expression of GCMB by intrathymic parathyroid hormone-secreting adenomas indicates their parathyroid cell origin.

GCMA and GCMB are related transcription factors that are critically important for embryological development of the placenta and parathyroid glands, respectively. Mice in which parathyroid glands have been surgically removed or fail to develop due to genetic loss of GCMB show continued production of PTH from a subset of thymic cells that express GCMA. In this study we examined whether human thymus produces PTH and/or GCMA and whether intrathymic PTH-secreting adenomas express GCMA or GCMB to determine the embryological origin of the secretory cells.

Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal imprinting at GNAS1.

Although the molecular basis of pseudohypoparathyroidism type 1b (PHP type 1b) remains unknown, a defect in imprinting at the GNAS1 locus has been suggested by the consistent finding of paternal-specific patterns of DNA methylation on maternally inherited GNAS1 alleles. To characterize the relationship between the genetic and epigenetic defects in PHP type 1b, we analyzed allelic expression and methylation of CpG islands within exon 1A of GNAS1 in patients with sporadic PHP type 1b and in affected and unaffected individuals from five multigenerational kindreds with PHP type 1b. All subjects with resistance to parathyroid hormone (PTH) showed loss of methylation of the exon 1A region on the maternal GNAS1 allele and/or biallelic expression of exon 1A-containing transcripts, consistent with an imprinting defect.

Ambiguous genitalia with perineoscrotal hypospadias in 46,XY individuals: long-term medical, surgical, and psychosexual outcome.

Objectives: To identify and study adults (21 years or older) who have a 46,XY karyotype and presented as infants or children with genital ambiguity, including a small phallus and perineoscrotal hypospadias, reared male or female.

Methods: Participants were classified according to the cause underlying their intersex condition based on review of medical and surgical records. Long-term medical and surgical outcome was assessed with a written questionnaire and physical examination.

Neonatal hypocalcemic seizures: case report and literature review.

Seizures during the neonatal period have a broad differential diagnosis, many with a specific treatment and prognosis. In the case reported, a combination of dietary and endocrinologic abnormalities resulted in hypocalcemic seizures, which continued despite aggressive correction of serum ionized calcium levels. Serial electroencephalograms (EEG) performed during the hospitalization were markedly abnormal, and treatment with anticonvulsant drugs was considered given the persistence of seizures despite normalization of serum calcium levels.