Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
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CIF B-96337217


Growth hormone, IA, IB, II and III, isolated deficiency ... types, (pituitary dwarfism) (Isolated growth hormone deficiency - IGHD-) - Genes BTK, GH1 and GHRHR

Growth hormone (GH: Growth Hormone) is a multifunctional hormone produced in the anterior pituitary gland that promotes post - natal growth of skeletal and soft tissues. The pathology due to GH deficiency called pituitary dwarfism or isolated growth hormone deficiency (IGHD: Isolated GH deficiency), whereas when affected other hormones of the anterior pituitary (TSH, LH / FSH , PRL and ACTH) is called combined pituitary hormone deficiency (CPHD: Pitutary combined hormone deficiency).

Described four types of isolated hormone deficiency growth differentiated by gravity, the gene involved, and the inheritance pattern. The type IA (IGHD IA) is due to an absence of growth hormone and is the most serious of all types. In individuals with type IA, lack of growth is evident at birth. People with type IB (IB IGHD) produce very low amounts of growth hormone. As a result, the IB type is characterized by short stature, but this growth defect is not as serious as in IA type, so stunting usually apparent in early childhood or middle. Individuals with type II (IGHD II) have very low growth hormone statureUkrainian amounts that varies in severity. In these individuals stunting it is usually evident in early or middle childhood. It is estimated that nearly half of individuals with Type II have underdeveloped pituitary (hypophysis hypoplastic). For its part, the type III (IGHD III) is similar to type II, except for people with type III can also have a weakened immune system and are prone to frequent infections. These individuals produce very few B cells and is associated with agammaglobulinemia.

Isolated growth hormone deficiency is due to mutations in one of at least three genes. IGHD IA and types IGHD II are due to mutations in the GH1 gene, type IB IGHD mutations in the GH1 gene or GHRHR, and IGHD type III is due to mutations in the BTK gene.

The GH1 gene, located on the long arm of chromosome 17 (17q24.2), encoding the protein of growth hormone (GH). Growth hormone is produced in the pituitary gland and plays an important role in promoting the growth of the organism. Growth hormone also plays a role in various metabolic processes in the body. They have identified more than 70 mutations in the GH1 gene responsible for IGHD types IA, IB and IGHD IGHD II. Mutations in the GH1 gene coding inhibit or hinder the growth hormone. Without enough growth hormone, the body fails to grow at its normal pace, causing slow growth and short stature. The most severe form of IGHD (IGHD IA), characterized by the total absence of GH and patients carry deletions in the entire gene, mutations or mutations leading to a premature stop codon. In addition, often they develop anti-GH antibodies upon exogenous GH treatment. Milder forms are characterized by very little GH, but detectable, and a positive response to exogenous GH therapy. Included therein the IGHD IB, which is the most common form, and IGHD II. Mutations in patients with these latter forms are due to nucleotide substitutions that affect mRNA.

GHRHR gene, located on the short arm of chromosome 7 (7p14), encodes the hormone receptor GH. Binding releasing hormone growth hormone receptor triggers encoding growth hormone and its release from the pituitary gland. They described more than 20 mutations in the gene responsible for IGHD GHRHR IB. Mutations in the gene GHRHR adversely affect coding or release of growth hormone. Resulting deficiency of growth hormone prevents the organism to grow at the expected rate.

Finally, the BTK gene, located on the long arm of the X (Xq21.33-q22) chromosome, encodes a protein called Bruton 's tyrosine kinase (BTK), which is essential for the development and maturation of B cells BTK protein transmits chemical signals that induce B cells to mature and produce antibodies. BTK mutations responsible IGHD III result encoding a nonfunctional version of the BTK protein. These individuals are prone to infections, because they produce very few B cells and are deficient antibody (agammaglobulinemia). Although BTK protein deficiency is responsible for the symptoms of the immune system, however it is unclear how mutations in the BTK gene contribute to short stature in people with IGHD III.

Some people with isolated growth hormone deficiency have mutations in BTK, GH1 or GHRHR genes. In these people, the cause of the disease is unknown. When IGHD has not identified genetic cause, the process is called isolated deficiency idiopathic growth hormone.

Isolated growth hormone deficiency can have different inheritance patterns depending on the type. IGHD IA and types IGHD IB are inherited in an autosomal recessive pattern, which means that both copies of the GH1 gene or GHRHR in each cell have mutations. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. IGHD II can be inherited in an autosomal dominant pattern, meaning that a mutation in the GH1 gene copy in each cell is sufficient to express the disease. IGHD II may also be due to new mutations in the GH1 gene and occur in people with no history of disease in your family. Finally, IGHD III, it due to mutations in the BTK gene is inherited in a recessive pattern linked to chromosome X. In males, who have only one X chromosome, an altered copy of the gene in each cell is sufficient to express the disease. In females, having two X chromosomes, a mutation would have to occur in both copies of the gene to express the alteration. Because it is unlikely that women have two altered copies of this gene, males are affected by recessive X - linked disorders much more frequently than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome.

Tests in IVAMI: in IVAMI perform detection of mutations associated with isolated growth hormone deficiency, by complete PCR amplification of the exons of BTK, GH1 and GHRHR genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).