Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
J Vet Intern Med. 2022 Sep;36(5):1597-1606. doi: 10.1111/jvim.16524. Epub 2022 Aug 26.
Primary congenital hypothyroidism (CH) is a rare endocrine disorder in cats with a largely unknown genetic cause.
Describe the clinical presentation of CH in 11 affected cats and identify the causal genetic variant.
Eleven CH-cats from 10 unrelated families, 11 CH-free family members, 21 unrelated CH-free cats, and 155 unrelated nondiagnosed cats from different breeds.
Case control study of CH-cats and their siblings (2019-2021). Diagnosis was based on low to low-normal serum thyroxine (T4) concentrations, high thyroid-stimulating hormone (TSH) concentrations and clinical signs compatible with CH. We identified the causal variant using Sanger sequencing, genotyping via PCR-RFLP and variant interpretation using ACMG/AMP guidelines.
All CH-cats (5 weeks-8 years) had disproportionate dwarfism. A goiter was not palpable in all. Thyroid scintigraphy with radiopertechnetate showed abnormally high uptake by thyroid glands, whereas scintigraphy with radioiodine showed abnormally low uptake, compatible with a defect in iodine organification by thyroid peroxidase (TPO). All cases were homozygous for TPO variant XM_006930524.4:c.430G>A(p.(Gly144Arg)), while none of the CH-free cats were. All sampled parents were heterozygous for this recessive variant. This variant was found in 15 cat breeds with an estimated allele frequency of 9%.
Disproportionate dwarfism, abnormally high TSH and abnormally low to low-normal T4 concentrations are diagnostic for CH in cats. All cases had dyshormonogenesis demonstrated by thyroid scintigraphy. This novel TPO missense variant (not described in humans) causes CH in cats and awareness of it can assist in diagnosis and breeding.
先天性甲状腺功能减退症（CH）是一种罕见的猫内分泌疾病，其遗传原因尚不清楚。
描述 11 例 CH 猫的临床表现，并确定其致病的遗传变异。
10 个无亲缘关系的 CH 猫家庭中的 11 只 CH 猫、11 只无亲缘关系的 CH 猫正常对照、21 只无亲缘关系的 CH 猫正常对照和 155 只不同品种的无诊断的猫。
对 2019 年至 2021 年的 CH 猫及其兄弟姐妹进行病例对照研究。诊断基于低至正常低值的血清甲状腺素（T4）浓度、高甲状腺刺激激素（TSH）浓度和符合 CH 的临床症状。我们使用 Sanger 测序、PCR-RFLP 基因分型和 ACMG/AMP 指南进行变异解释来确定致病变异。
所有 CH 猫（5 周龄-8 岁）均存在不成比例的侏儒症。所有猫均无法触及甲状腺肿。放射性锝甲状腺闪烁扫描显示甲状腺摄取异常增高，而放射性碘闪烁扫描显示摄取异常降低，这与甲状腺过氧化物酶（TPO）的碘有机化缺陷相符。所有病例均为 TPO 变异 XM_006930524.4:c.430G>A(p.(Gly144Arg))纯合子，而无 CH 猫为纯合子。所有受检的父母均为该隐性变异的杂合子。该变异在 15 个猫品种中发现，估计等位基因频率为 9%。
不成比例的侏儒症、异常高的 TSH 和异常低至正常低值的 T4 浓度是猫 CH 的诊断标准。所有病例的甲状腺闪烁扫描均显示激素生成障碍。这种新的 TPO 错义变异（在人类中未描述）导致猫 CH，并提高对其的认识可以辅助诊断和繁殖。
