Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Hospital Escuela de Medicina Veterinaria, Unidad de Endocrinología, Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Hospital Escuela de Medicina Veterinaria, Unidad de Endocrinología, Buenos Aires, Argentina.
Domest Anim Endocrinol. 2018 Oct;65:1-8. doi: 10.1016/j.domaniend.2018.04.005. Epub 2018 Apr 24.
An iodide transport defect (ITD) in the thyroid gland was determined to cause congenital dyshormonogenic hypothyroidism with goiter (CDHG) in 2 members of a family of Shih-Tzu dogs. Strikingly, both dogs were also diagnosed with dilated cardiomyopathy at 24 and 1.5 mo of age. The only sign of hypothyroidism was a moderate growth delay in the adult dog. The ITD was recognized by the absence of uptake of technetium-99m in the salivary glands (sg) and goiter observed by scintigraphy. In the same scan, radiopharmaceutical uptake was found in the anterior mediastinum of both dogs and in the right axillary lymph node in the oldest dog. A follicular thyroid carcinoma was diagnosed by histopathology after thyroidectomy of the older dog. An adenomatous goiter with ectopic thyroid tissue, and degenerative changes in myocardium were the findings after necropsy in the youngest dog. A homozygous mutation of the intron 9 splice acceptor site of SLC5A5 gene, encoding the sodium/iodine symporter (NIS), was found in the DNA of one of the affected dogs. The mutation was a single base transition of guanine > adenine (G > A) at position 45,024,672 of dog chromosome 20 (CFA20). Five of eight healthy dogs, including both parents of one of the dogs exhibiting CDHG, were heterozygous A/G, and the other 3 were homozygous for the wild-type allele G/G. No sequence variant was found in thyroid peroxidase of the affected dog. Congenital dyshormonogenic hypothyroidism with goiter in this family is an autosomal recessive trait. Our findings are the first evidence of an SLC5A5 mutation in dogs and establish a new genetic cause of CDHG.
甲状腺碘转运缺陷（ITD）被确定为导致 2 只西施犬家族成员发生先天性甲状腺机能减退伴甲状腺肿（CDHG）的原因。引人注目的是，这两只狗在 24 月龄和 1.5 月龄时还被诊断出患有扩张型心肌病。唯一的甲状腺功能减退迹象是成年犬生长发育迟缓。通过唾液腺（sg）和闪烁扫描观察到的甲状腺肿中锝-99m 摄取缺失，识别出 ITD。在同一扫描中，发现两只狗的前纵隔和最老的狗的右侧腋窝淋巴结中摄取放射性药物。对较老的狗进行甲状腺切除术，通过组织病理学诊断为滤泡状甲状腺癌。对最小的狗进行尸检后，发现为腺瘤性甲状腺肿伴异位甲状腺组织和心肌退行性变。在受影响的狗的 DNA 中发现了 SLC5A5 基因（编码钠/碘转运体（NIS））内含子 9 剪接受体位点的纯合突变，该突变是第 45,024,672 位碱基鸟嘌呤>腺嘌呤（G > A）的单碱基转换，在狗染色体 20（CFA20）上。8 只健康犬中有 5 只是杂合子 A/G，包括患有 CDHG 的其中一只狗的父母，另外 3 只是野生型等位基因 G/G 的纯合子。受影响的狗的甲状腺过氧化物酶未发现序列变异。该家族的先天性甲状腺机能减退伴甲状腺肿是一种常染色体隐性遗传特征。我们的发现是犬 SLC5A5 突变的首例证据，并确立了 CDHG 的新遗传原因。
