Investigation of relationship of the mitochondrial DNA 16189 T>C polymorphism with metabolic syndrome and its associated clinical parameters in Turkish patients.

Objective: Mitochondrial DNA (mtDNA) polymorphisms have been implicated in the pathophysiology of human diseases. Among them, a T>C nucleotide transition on the 16189 nucleotide position of mtDNA has been studied in several metabolic diseases including diabetes and obesity. In this study we aimed to investigate the association of this polymorphism among Turkish metabolic syndrome patients.

Mitochondrial DNA common deletion is not associated with thyroid, breast and colorectal tumors in Turkish patients.

Recently, efforts have been focused on mitochondrial DNA changes and their relation to human cancers. Among them, a 4977 bp deletion of mitochondrial DNA, named "common deletion", has been investigated in several types of tumors, with inconsistent results. In this study, we investigated the presence of the common deletion in tissues from 25 breast, 25 colorectal and 50 thyroid tumors and in the adjacent healthy tissues from Turkish patients.

The effect of subclinical hypothyroidism on platelet parameters.

Background: Hypothyroidism has a broad clinical spectrum. Today, physicians frequently encounter patients with very mild thyroid dysfunction instead of overt hypothyroidism. These patients have normal serum levels of thyroxine and triiodothyronine and only mildly elevated serum thyrotropin levels.

Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years' experience.

Context: Primary adrenal failure is a life-threatening condition that can be caused by a range of etiologies, including autoimmune, metabolic, and developmental disorders. The nuclear receptors DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) play an important role in adrenal development and function, and mutations in these transcription factors have been found in patients with adrenal hypoplasia.

Objective: Our objective was to investigate the prevalence of DAX1 and SF1 mutations in children and adults with primary adrenal failure of unknown etiology (i.

Battle of the sexes: new insights into genetic pathways of gonadal development.

Sex determination is governed by a series of genetic switches that influence cell fate and differentiation during critical periods of gonadal development. Remarkably, the primordial fetal gonad is bipotential. Therefore, gonadal development provides an excellent opportunity to identify genes involved in differential organogenesis.

SF1 in the development of the adrenal gland and gonads.

SF1 (steroidogenic factor-1; NR5A1) is an orphan nuclear receptor that is expressed in the adrenal gland, gonads, spleen, ventromedial hypothalamus and pituitary gonadotroph cells. Combined approaches of targeted mutagenesis in mice and examination of the effects of naturally occurring mutations in humans have clarified the role of SF1 in steroidogenesis and development. Targeted disruption of SF1 (FTZF1) in mice prevents gonadal and adrenal development and causes male-to-female sex reversal.

A novel single base deletion at codon 434 (1301delT) of the DAX1 gene associated with prepubertal testis enlargement.

We have identified a novel DAX1 frameshift mutation (1301delT) at codon 434 in a patient with primary adrenal insufficiency. This 11-day-old boy was admitted to the hospital with hyponatremia, hyperkalemia, and suspected congenital adrenal abnormality. He exhibited severe hypoglycemia, pallor of the skin, buccal and genital hyperpigmentation, hypotension (90/45 mm Hg), anemia, and diarrhea.

An alternate translation initiation site circumvents an amino-terminal DAX1 nonsense mutation leading to a mild form of X-linked adrenal hypoplasia congenita.

Mutations in DAX1 [dosage-sensitive sex reversal-adrenal hypoplasia congenita (AHC) critical region on the X chromosome gene 1; NR0B1] cause X-linked AHC, a disease characterized by primary adrenal failure in infancy or childhood and reproductive abnormalities later in life. Most of these patients have nonsense or frameshift mutations that cause premature truncation of the DAX1 protein, thereby eliminating its transcriptional silencing activity. We evaluated a patient with an unusual form of AHC manifest as late-onset adrenal insufficiency and gonadal failure.

The role of SF1 in adrenal and reproductive function: insight from naturally occurring mutations in humans.

Steroidogenic factor 1 is a monomeric orphan nuclear receptor and one of several hundreds of transcription factors encoded in the human genome. It regulates the transcription of many genes involved in gonadal development, sexual differentiation, steroidogenesis and reproduction. Recently, mutations in the gene encoding SF1 have been identified in several patients with primary adrenal failure and 46,XY sex-reversal.

Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner.

The orphan nuclear receptor steroidogenic factor-1 (SF-1, NR5A1) regulates the transcription of multiple genes involved in steroidogenesis, reproduction, and male sexual differentiation. A heterozygous loss-of-function SF-1 mutation (G35E) has been described in a patient with adrenal failure and complete 46XY sex-reversal, indicating that haploinsufficiency of this factor is sufficient to cause a severe clinical phenotype. This mutation in the P-box region of the DNA-binding domain markedly impairs SF-1 binding to most response elements.

Hypogonadotropic hypogonadism as a presenting feature of late-onset X-linked adrenal hypoplasia congenita.

Mutations in the orphan nuclear receptor DAX-1 cause X-linked adrenal hypoplasia congenita. Affected boys usually present with primary adrenal failure in early infancy or childhood. Impaired sexual development because of hypogonadotropic hypogonadism becomes apparent at the time of puberty.