Tonacchera M, Perri A, De Marco G, Agretti P, Montanelli L, Banco M E, Corrias A, Bellone J, Tosi M T, Vitti P, Martino E, Pinchera A, Chiovato L
Dipartimento di Endocrinologia e Metabolismo, Università di Pisa, Pisa, Italy.
J Endocrinol Invest. 2003 Oct;26(10):997-1000. doi: 10.1007/BF03348198.
The prevalence of thyroid diseases in children with Down's syndrome (DS) is about 3%. The most frequently observed condition is autoimmune subclinical hypothyroidism (SH). Autoimmune SH must be distinguished from defects in the biological activity of the TSH molecule or from the rare inherited condition of thyroid resistance to TSH. To investigate this last aspect we studied 12 patients with DS that had moderately elevated TSH with normal free thyroid hormones without signs of autoimmunity. For the genetic analysis the genomic DNA was extracted from peripheral lymphocytes. All the exons of the TSH receptor (TSHr) and Gs(alpha) genes were sequenced. The genetic analysis of the TSHr gene revealed the presence of four polymorphic variants. In two patients there was an allelic variant in the exon 1 (Pro52Thr--in one patient in the heterozygous state and in the other as a homozygous substitution). In one patient there was an allelic variant in the exon 1 (Asp36His) in the heterozygous state. In 11 patients there was a silent polymorphism in the exon 7 at nucleotide 561. All patients were homozygous for a silent polymorphism in the exon 9 at nucleotide 855. No inactivating mutations of TSHr or Gs(alpha) genes were identified in the 12 patients. In conclusion, our results seem to exclude the role of TSHr or Gs(alpha) gene mutations in the pathogenesis of the non-autoimmune SH observed in some children with DS.
唐氏综合征（DS）患儿甲状腺疾病的患病率约为3%。最常见的情况是自身免疫性亚临床甲状腺功能减退症（SH）。必须将自身免疫性SH与促甲状腺激素（TSH）分子生物活性缺陷或罕见的遗传性甲状腺对TSH抵抗相区分。为了研究这最后一个方面，我们对12例TSH中度升高、游离甲状腺激素正常且无自身免疫迹象的DS患者进行了研究。为进行基因分析，从外周淋巴细胞中提取基因组DNA。对TSH受体（TSHr）和Gs（α）基因的所有外显子进行测序。TSHr基因的基因分析显示存在四个多态性变体。在两名患者中，外显子1存在等位基因变体（Pro52Thr——一名患者为杂合状态，另一名患者为纯合替代）。在一名患者中，外显子1存在杂合状态的等位基因变体（Asp36His）。在11名患者中，外显子7在核苷酸561处存在沉默多态性。所有患者外显子9在核苷酸855处的沉默多态性均为纯合子。在这12名患者中未发现TSHr或Gs（α）基因的失活突变。总之，我们的结果似乎排除了TSHr或Gs（α）基因突变在一些DS患儿非自身免疫性SH发病机制中的作用。
