Familial growth hormone deficiency with mutated GHRH receptor gene

Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha

César Y. Hayashida, Rogério G. Gondo, Carmela Ferrari, Sérgio P A Toledo, Roberto Salvatori, Michael A. Levine, Marilza C L Ezabella, Neusa Abelin, Daniel Gianella-Neto, Bernardo L. Wajchenberg

Research output: Contribution to journalArticle

Abstract

Objective: To characterize clinically and hormonally the syndrome of autosomal recessive familial growth hormone deficiency (FGHD) recently identified in Itabaianinha, Sergipe, Brazil, caused by a novel mutation (mt) that inactivates the growth hormone-releasing hormone receptor (GHRH-R) gene. Design: Clinical and hormonal evaluations were performed in 21 FGHD individuals (mt/mt group) aged 8 to 63 years, 13 heterozygotes for the GHRH-R mutation (wt/mt group) and 5 homozygotes for the wild type (wt) allele (wt/wt group), identified by genotyping of peripheral blood leukocyte DNA. Methods: Clinical and hormonal characterization included physical examination and measurement of GH, IGF-I, IGF binding protein-3 (IGFBP-3), cortisol, prolactin, LH, FSH, and free thyroxine (FT4). Results: Clinical features were consistent with isolated growth hormone deficiency. Height was significantly reduced in the mt/mt group compared with the wt/mt group (mean height standard deviation score (SDS) ± S.D.: -7.35 ± 1.37 vs -1.84 ± 1.44 respectively, P <0.0001), and the wt/wt group (-1.85 ± 0.81, P = 0.0007). The height of the 13 wt/mt subjects did not differ from the 5 wt/wt individuals. Serum GH, IGF-I, IGF-I SDS, IGFBP-3 and IGFBP-3 SDS were all significantly lower in the mt/mt group than in the wt/mt and wt/wt groups. Two affected children treated with GH for 1 year showed a normal growth response. Serum IGF-I and IGF-I SDS were lower in wt/mt compared with wt/wt group, but did not reach statistical significance. IGF-I and IGF-I SDS correlated inversely with age in wt/mt group. Conclusions: FGHD due to an autosomal recessive GHRH-R gene mutation leads to marked dwarfism, phenotypically and hormonally indistinguishable from other forms of isolated GH deficiency. Heterozygotes for the GHRH-R mutation appear to have a partial defect in the GH/IGF axis, with no apparent height impairment.

Original languageEnglish (US)
Pages (from-to)557-563
Number of pages7
JournalEuropean Journal of Endocrinology
Volume142
Issue number6
StatePublished - Jun 2000

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Growth Hormone
Mutation
Genes
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 3
Pituitary Dwarfism
somatotropin releasing hormone receptor
Heterozygote
Dwarfism
Homozygote
Serum
Thyroxine
Prolactin
Physical Examination
Brazil
Hydrocortisone
Leukocytes
Alleles

ASJC Scopus subject areas

  • Endocrinology

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Familial growth hormone deficiency with mutated GHRH receptor gene : Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha. / Hayashida, César Y.; Gondo, Rogério G.; Ferrari, Carmela; Toledo, Sérgio P A; Salvatori, Roberto; Levine, Michael A.; Ezabella, Marilza C L; Abelin, Neusa; Gianella-Neto, Daniel; Wajchenberg, Bernardo L.

In: European Journal of Endocrinology, Vol. 142, No. 6, 06.2000, p. 557-563.

Research output: Contribution to journalArticle

Hayashida, CY, Gondo, RG, Ferrari, C, Toledo, SPA, Salvatori, R, Levine, MA, Ezabella, MCL, Abelin, N, Gianella-Neto, D & Wajchenberg, BL 2000, 'Familial growth hormone deficiency with mutated GHRH receptor gene: Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha', European Journal of Endocrinology, vol. 142, no. 6, pp. 557-563.
Hayashida, César Y. ; Gondo, Rogério G. ; Ferrari, Carmela ; Toledo, Sérgio P A ; Salvatori, Roberto ; Levine, Michael A. ; Ezabella, Marilza C L ; Abelin, Neusa ; Gianella-Neto, Daniel ; Wajchenberg, Bernardo L. / Familial growth hormone deficiency with mutated GHRH receptor gene : Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha. In: European Journal of Endocrinology. 2000 ; Vol. 142, No. 6. pp. 557-563.
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title = "Familial growth hormone deficiency with mutated GHRH receptor gene: Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha",
abstract = "Objective: To characterize clinically and hormonally the syndrome of autosomal recessive familial growth hormone deficiency (FGHD) recently identified in Itabaianinha, Sergipe, Brazil, caused by a novel mutation (mt) that inactivates the growth hormone-releasing hormone receptor (GHRH-R) gene. Design: Clinical and hormonal evaluations were performed in 21 FGHD individuals (mt/mt group) aged 8 to 63 years, 13 heterozygotes for the GHRH-R mutation (wt/mt group) and 5 homozygotes for the wild type (wt) allele (wt/wt group), identified by genotyping of peripheral blood leukocyte DNA. Methods: Clinical and hormonal characterization included physical examination and measurement of GH, IGF-I, IGF binding protein-3 (IGFBP-3), cortisol, prolactin, LH, FSH, and free thyroxine (FT4). Results: Clinical features were consistent with isolated growth hormone deficiency. Height was significantly reduced in the mt/mt group compared with the wt/mt group (mean height standard deviation score (SDS) ± S.D.: -7.35 ± 1.37 vs -1.84 ± 1.44 respectively, P <0.0001), and the wt/wt group (-1.85 ± 0.81, P = 0.0007). The height of the 13 wt/mt subjects did not differ from the 5 wt/wt individuals. Serum GH, IGF-I, IGF-I SDS, IGFBP-3 and IGFBP-3 SDS were all significantly lower in the mt/mt group than in the wt/mt and wt/wt groups. Two affected children treated with GH for 1 year showed a normal growth response. Serum IGF-I and IGF-I SDS were lower in wt/mt compared with wt/wt group, but did not reach statistical significance. IGF-I and IGF-I SDS correlated inversely with age in wt/mt group. Conclusions: FGHD due to an autosomal recessive GHRH-R gene mutation leads to marked dwarfism, phenotypically and hormonally indistinguishable from other forms of isolated GH deficiency. Heterozygotes for the GHRH-R mutation appear to have a partial defect in the GH/IGF axis, with no apparent height impairment.",
author = "Hayashida, {C{\'e}sar Y.} and Gondo, {Rog{\'e}rio G.} and Carmela Ferrari and Toledo, {S{\'e}rgio P A} and Roberto Salvatori and Levine, {Michael A.} and Ezabella, {Marilza C L} and Neusa Abelin and Daniel Gianella-Neto and Wajchenberg, {Bernardo L.}",
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T1 - Familial growth hormone deficiency with mutated GHRH receptor gene

T2 - Clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha

AU - Hayashida, César Y.

AU - Gondo, Rogério G.

AU - Ferrari, Carmela

AU - Toledo, Sérgio P A

AU - Salvatori, Roberto

AU - Levine, Michael A.

AU - Ezabella, Marilza C L

AU - Abelin, Neusa

AU - Gianella-Neto, Daniel

AU - Wajchenberg, Bernardo L.

PY - 2000/6

Y1 - 2000/6

N2 - Objective: To characterize clinically and hormonally the syndrome of autosomal recessive familial growth hormone deficiency (FGHD) recently identified in Itabaianinha, Sergipe, Brazil, caused by a novel mutation (mt) that inactivates the growth hormone-releasing hormone receptor (GHRH-R) gene. Design: Clinical and hormonal evaluations were performed in 21 FGHD individuals (mt/mt group) aged 8 to 63 years, 13 heterozygotes for the GHRH-R mutation (wt/mt group) and 5 homozygotes for the wild type (wt) allele (wt/wt group), identified by genotyping of peripheral blood leukocyte DNA. Methods: Clinical and hormonal characterization included physical examination and measurement of GH, IGF-I, IGF binding protein-3 (IGFBP-3), cortisol, prolactin, LH, FSH, and free thyroxine (FT4). Results: Clinical features were consistent with isolated growth hormone deficiency. Height was significantly reduced in the mt/mt group compared with the wt/mt group (mean height standard deviation score (SDS) ± S.D.: -7.35 ± 1.37 vs -1.84 ± 1.44 respectively, P <0.0001), and the wt/wt group (-1.85 ± 0.81, P = 0.0007). The height of the 13 wt/mt subjects did not differ from the 5 wt/wt individuals. Serum GH, IGF-I, IGF-I SDS, IGFBP-3 and IGFBP-3 SDS were all significantly lower in the mt/mt group than in the wt/mt and wt/wt groups. Two affected children treated with GH for 1 year showed a normal growth response. Serum IGF-I and IGF-I SDS were lower in wt/mt compared with wt/wt group, but did not reach statistical significance. IGF-I and IGF-I SDS correlated inversely with age in wt/mt group. Conclusions: FGHD due to an autosomal recessive GHRH-R gene mutation leads to marked dwarfism, phenotypically and hormonally indistinguishable from other forms of isolated GH deficiency. Heterozygotes for the GHRH-R mutation appear to have a partial defect in the GH/IGF axis, with no apparent height impairment.

AB - Objective: To characterize clinically and hormonally the syndrome of autosomal recessive familial growth hormone deficiency (FGHD) recently identified in Itabaianinha, Sergipe, Brazil, caused by a novel mutation (mt) that inactivates the growth hormone-releasing hormone receptor (GHRH-R) gene. Design: Clinical and hormonal evaluations were performed in 21 FGHD individuals (mt/mt group) aged 8 to 63 years, 13 heterozygotes for the GHRH-R mutation (wt/mt group) and 5 homozygotes for the wild type (wt) allele (wt/wt group), identified by genotyping of peripheral blood leukocyte DNA. Methods: Clinical and hormonal characterization included physical examination and measurement of GH, IGF-I, IGF binding protein-3 (IGFBP-3), cortisol, prolactin, LH, FSH, and free thyroxine (FT4). Results: Clinical features were consistent with isolated growth hormone deficiency. Height was significantly reduced in the mt/mt group compared with the wt/mt group (mean height standard deviation score (SDS) ± S.D.: -7.35 ± 1.37 vs -1.84 ± 1.44 respectively, P <0.0001), and the wt/wt group (-1.85 ± 0.81, P = 0.0007). The height of the 13 wt/mt subjects did not differ from the 5 wt/wt individuals. Serum GH, IGF-I, IGF-I SDS, IGFBP-3 and IGFBP-3 SDS were all significantly lower in the mt/mt group than in the wt/mt and wt/wt groups. Two affected children treated with GH for 1 year showed a normal growth response. Serum IGF-I and IGF-I SDS were lower in wt/mt compared with wt/wt group, but did not reach statistical significance. IGF-I and IGF-I SDS correlated inversely with age in wt/mt group. Conclusions: FGHD due to an autosomal recessive GHRH-R gene mutation leads to marked dwarfism, phenotypically and hormonally indistinguishable from other forms of isolated GH deficiency. Heterozygotes for the GHRH-R mutation appear to have a partial defect in the GH/IGF axis, with no apparent height impairment.

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