Novel growth hormone-releasing hormone receptor gene mutations in Turkish children with isolated growth hormone deficiency. 2014

Ahmet Arman, and Bumin Nuri Dündar, and Ergun Çetinkaya, and Nilüfer Erzaim, and Atilla Büyükgebiz
Marmara University Faculty of Medicine, Department of Medical Genetics, İstanbul, Turkey. E-ma-il: ahmetarman@marmara.edu.tr.

OBJECTIVE Isolated growth hormone deficiency (IGHD) is defined as a medical condition associated with growth failure due to insufficient production of GH or lack of GH action. Mutations in the gene encoding for GH-releasing hormone receptor (GHRHR) have been detected in patients with IGHD type IB. However, genetic defects on GHRHR causing IGHD in the Turkish population have not yet been reported. To identify mutations on GHRHR gene in a population of Turkish children with IGHD. METHODS Ninety-six Turkish children with IGHD were included in this study. Exon1-13 and exon/intron boundaries of GHRHR were amplified by suitable primers. The polymerase chain reaction products for GHRHR gene were sequenced with primers. RESULTS We analyzed the GHRHR gene for mutations in ninety-six patients with IGHD based on sequence results. We identified novel p.K264E, p.S317T, p.S330L, p.G369V, p.T257A and C base insertion on position 380 (c.380inserC) mutations. In 5 of the patients, the mutation was homozygote and in 1-heterozygote (p.S317T). CONCLUSIONS Six new missense mutations and one first case of insertion mutations for the GHRHR gene are reported.

UI MeSH Term Description Entries
D008297 Male Males
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D004393 Dwarfism, Pituitary A form of dwarfism caused by complete or partial GROWTH HORMONE deficiency, resulting from either the lack of GROWTH HORMONE-RELEASING FACTOR from the HYPOTHALAMUS or from the mutations in the growth hormone gene (GH1) in the PITUITARY GLAND. It is also known as Type I pituitary dwarfism. Human hypophysial dwarf is caused by a deficiency of HUMAN GROWTH HORMONE during development. Growth Hormone Deficiency Dwarfism,Hypophysial Dwarf,Hyposomatotrophic Dwarfism,Pituitary Dwarf,Dwarfism, Growth Hormone Deficiency,Isolated GH Deficiency,Isolated Growth Hormone Deficiency,Isolated HGH Deficiency,Isolated Human Growth Hormone Deficiency,Isolated Somatotropin Deficiency,Isolated Somatotropin Deficiency Disorder,Nanism, Pituitary,Pituitary Dwarfism,Pituitary Nanism
D005091 Exons The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA. Mini-Exon,Exon,Mini Exon,Mini-Exons
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014421 Turkey Country in Southeastern Europe and Southwestern Asia bordering the Black Sea, between Bulgaria and Georgia, and bordering the Aegean Sea and the Mediterranean Sea, between Greece and Syria. The capital is Ankara. Turkiye
D016254 Mutagenesis, Insertional Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation. Gene Insertion,Insertion Mutation,Insertional Activation,Insertional Mutagenesis,Linker-Insertion Mutagenesis,Mutagenesis, Cassette,Sequence Insertion,Viral Insertional Mutagenesis,Activation, Insertional,Activations, Insertional,Cassette Mutagenesis,Gene Insertions,Insertion Mutations,Insertion, Gene,Insertion, Sequence,Insertional Activations,Insertional Mutagenesis, Viral,Insertions, Gene,Insertions, Sequence,Linker Insertion Mutagenesis,Mutagenesis, Linker-Insertion,Mutagenesis, Viral Insertional,Mutation, Insertion,Mutations, Insertion,Sequence Insertions
D018013 Receptors, Neuropeptide Cell surface receptors that bind specific neuropeptides with high affinity and trigger intracellular changes influencing the behavior of cells. Many neuropeptides are also hormones outside of the nervous system. Neuropeptide Receptors,Neuropeptide Receptor,Receptors, Neuropeptides,Neuropeptides Receptors,Receptor, Neuropeptide
D018017 Receptors, Pituitary Hormone-Regulating Hormone Cell surface receptors that bind the hypothalamic hormones regulating pituitary cell differentiation, proliferation, and hormone synthesis and release, including the pituitary-releasing and release-inhibiting hormones. The pituitary hormone-regulating hormones are also released by cells other than hypothalamic neurons, and their receptors also occur on non-pituitary cells, especially brain neurons, where their role is less well understood. Receptors for dopamine, which is a prolactin release-inhibiting hormone as well as a common neurotransmitter, are not included here. Hypothalamic Release-Inhibiting Hormone Receptors,Hypothalamic Releasing Hormone Receptors,Pituitary Hormone-Regulating Hormone Receptors,Pituitary Hormone-Releasing Hormone Receptors,Receptors, Hypothalamic Release-Inhibiting Hormones,Receptors, Hypothalamic Releasing Hormones,Receptors, Pituitary Hormone Release Inhibiting Hormones,Receptors, Pituitary Hormone-Releasing Hormone,Hypothalamic Release Inhibiting Hormone Receptors,Pituitary Hormone Regulating Hormone Receptors,Pituitary Hormone Releasing Hormone Receptors,Receptors, Hypothalamic Release Inhibiting Hormones,Receptors, Pituitary Hormone Regulating Hormone,Receptors, Pituitary Hormone Releasing Hormone

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