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Computational Investigation of Growth Hormone Receptor Trp169Arg Heterozygous Mutation in a Child With Short Stature
Author(s) -
Porto William Farias,
Marques Felipe Albuquerque,
Pogue Huri Brito,
de Oliveira Cardoso Maria Teresinha,
do Vale Maria Gabriela Rodrigues,
da Silva Pires Állan,
Franco Octavio Luiz,
de Alencar Sérgio Amorim,
Pogue Robert
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26144
Subject(s) - growth hormone receptor , short stature , idiopathic short stature , dwarfism , mutant , biology , receptor , mutation , endocrinology , phenotype , growth hormone , gene , medicine , genetics , hormone
Mutations in the growth hormone receptor ( GHR ) gene can cause disruption of the growth hormone signaling pathway, resulting in growth deficiency due to growth hormone (GH) resistance. Both recessive and apparently dominant mutations have been described in the literature. In order to shed some light on the molecular mechanism of partial growth hormone resistance caused by heterozygous mutations, we performed an in‐depth in silico analysis of a mutation found in a girl with a previous diagnosis of idiopathic short stature. An array of algorithms was used to predict pathogenicity and potential impact on the protein, and molecular modeling, docking and dynamics were used to determine structural consequences. The results suggest that both of the possible single mutation‐containing heteromeric GH–GHR complexes, as well as the double GHR mutant complex result in perturbation of complex structures, with altered ability of the GHR dimers to interact with the GH peptide. J. Cell. Biochem. 118: 4762–4771, 2017. © 2017 Wiley Periodicals, Inc.