Neves Solange Caires, Mezalira Paola Rossi, Dias Vera M A, Chagas Antonio J, Viana Maria, Targovnik Hector, Knobel Meyer, Medeiros-Neto Geraldo, Rubio Ileana G S
Thyroid Unit, Cellular and Molecular Endocrinology Laboratory, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil.
Arq Bras Endocrinol Metabol. 2010 Nov;54(8):732-7. doi: 10.1590/s0004-27302010000800012.
The aim of this study was to identify the genetic defect of a patient with dyshormonogenetic congenital hypothyroidisms (CH) with total iodide organification defect (TIOD). A male child diagnosed with CH during neonatal screening. Laboratory tests confirmed the permanent and severe CH with TIOD (99% perchlorate release). The coding sequence of TPO, DUOX2, and DUOXA2 genes and 2957 base pairs (bp) of the TPO promoter were sequenced. Molecular analysis of patient's DNA identified the heterozygous duplication GGCC (c.1186_1187insGGCC) in exon 8 of the TPO gene. No additional mutation was detected either in the TPO gene, TPO promoter, DUOX2 or DUOXA2 genes. We have described a patient with a clear TIOD causing severe goitrous CH due to a monoallelic TPO mutation. A plausible explanation for the association between an autosomal recessive disorder with a single TPO-mutated allele is the presence of monoallelic TPO expression.
本研究的目的是确定一名患有激素生成障碍性先天性甲状腺功能减退症（CH）且伴有全碘有机化缺陷（TIOD）患者的基因缺陷。一名男童在新生儿筛查期间被诊断为CH。实验室检查证实为永久性重度CH伴TIOD（高氯酸盐释放率99%）。对TPO、DUOX2和DUOXA2基因的编码序列以及TPO启动子的2957个碱基对（bp）进行了测序。对患者DNA的分子分析确定了TPO基因第8外显子中的杂合重复GGCC（c.1186_1187insGGCC）。在TPO基因、TPO启动子、DUOX2或DUOXA2基因中未检测到其他突变。我们描述了一名因单等位基因TPO突变导致明显TIOD并引起重度甲状腺肿性CH的患者。对于常染色体隐性疾病与单个TPO突变等位基因之间关联的一个合理的解释是单等位基因TPO表达的存在。
