A Novel Intronic Pathogenic Variant in STAR With a Dominant Negative Mechanism Causes Attenuated Lipoid Congenital Adrenal Hyperplasia.
A Novel Intronic Pathogenic Variant in STAR With a Dominant Negative Mechanism Causes Attenuated Lipoid Congenital Adrenal Hyperplasia.
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DOI：
10.1177/23247096211014685
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发表时间：
2021-01
影响因子：
1.2
通讯作者：
Nokoff NJ
中科院分区：
文献类型：
--
作者：
Finn E;Kripps K;Chambers C;Rapp M;Meeks NJL;Xu F;Chen W;Larson AA;Nokoff NJ
类脂先天性肾上腺增生症（LCAH）通常是一种常染色体隐性遗传病。有 3 份报告称，具有显性作用杂合变异的个体会导致临床上显着的表型。我们报道了一名 46,XY 儿童，其 STAR 中存在新型杂合内含子变异，导致 LCAH 的生殖器表型减弱。患者出现新生儿低血糖，睾丸下降，阴囊和阴茎较小。评估显示原发性肾上腺皮质功能不全伴有皮质醇、醛固酮和雄激素缺乏。他被发现在 STAR 中具有从头杂合的新变体：c.65-2A>C。我们报告了一个新变异的病例，并对文献中同一位置的其他显性突变进行了回顾。临床医生应意识到 LCAH 生殖器表型减弱的可能性以及 c.65-2 STAR 中的新生变异对该表型发病机制的贡献。
Lipoid congenital adrenal hyperplasia (LCAH) is typically inherited as an autosomal recessive condition. There are 3 reports of individuals with a dominantly acting heterozygous variant leading to a clinically significant phenotype. We report a 46,XY child with a novel heterozygous intronic variant in STAR resulting in LCAH with an attenuated genital phenotype. The patient presented with neonatal hypoglycemia and had descended testes with a fused scrotum and small phallus. Evaluation revealed primary adrenal insufficiency with deficiencies of cortisol, aldosterone, and androgens. He was found to have a de novo heterozygous novel variant in STAR: c.65-2A>C. We report a case of a novel variant and review of other dominant mutations at the same position in the literature. Clinicians should be aware of the possibility of attenuated genital phenotypes of LCAH and the contribution of de novo variants in STAR at c.65-2 to the pathogenesis of that phenotype.