Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders

被引：40

作者：

Tusset, Cintia ^{[1
]}

Noel, Sekoni D. ^{[2
,3
]}

Trarbach, Ericka B. ^{[1
]}

Silveira, Leticia F. G. ^{[1
]}

Jorge, Alexander A. L. ^{[1
]}

Brito, Vinicius N. ^{[1
]}

Cukier, Priscila ^{[1
]}

Seminara, Stephanie B. ^{[4
,5
]}

de Mendonca, Berenice B. ^{[1
]}

Kaiser, Ursula B. ^{[2
,3
]}

Latronico, Ana Claudia ^{[1
]}

机构：

[1] Univ Sao Paulo, Fac Med, Lab Hormonios & Genet Mol LIM42, Unidade Endocrinol Desenvolvimento,Hosp Clin, Sao Paulo, Brazil

[2] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Harvard Ctr Reprod Sci, Boston, MA 02115 USA

[4] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Harvard Ctr Reprod Sci, Boston, MA 02114 USA

来源：

ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA | 2012年 / 56卷 / 09期

基金：

美国国家卫生研究院; 巴西圣保罗研究基金会;

关键词：

Neurokinin B; neurokinin B receptor; central precocious puberty; normosmic isolated hypogonadotropic hypogonadism; constitutional delay of growth and puberty; GONADOTROPIN-RELEASING-HORMONE; HYPOGONADOTROPIC HYPOGONADISM; NEUROKININ-B; TACHYKININ RECEPTORS; CONSTITUTIONAL DELAY; PROPEPTIDE MUTATION; ARCUATE NUCLEUS; REPRODUCTION; INHERITANCE; PATTERNS;

D O I：

10.1590/S0004-27302012000900008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. Subjects and methods: Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. Results: We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C > T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH. Conclusion: Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype. Arq Bras Endocrinol Metab. 2012; 56(9):646-52

引用

页码：646 / 652

页数：7

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