TY - JOUR
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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U2 - 10.1530/eje.0.1420557
DO - 10.1530/eje.0.1420557
M3 - Article
C2 - 10822217
AN - SCOPUS:0034086960
SN - 0804-4643
VL - 142
SP - 557
EP - 563
JO - European journal of endocrinology
JF - European journal of endocrinology
IS - 6
ER -