Monoallelic thyroid peroxidase gene mutation in a patient with congenital hypothyroidism with total iodide organification defect

Abstract

SUMMARYThe 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. Arq Bras Endocrinol Metab. 2010;54(8):732-7 SUMÁRIO O objetivo deste estudo foi identificar defeitos genéticos em paciente com hipotireoidismo congênito (HC) por disormonogênese e defeito total de incorporação de iodeto (DIIT). Neonato do sexo masculino com HC diagnosticado pelo rastreamento neonatal. Exames clínicos e radiológicos confirmaram que o paciente apresentava HC severo e permanente com DIIT (teste de perclorato: 99%). A região codificadora dos genes TPO, DUOX2, DUOXA2 e 2957 pares de bases (pb) do promotor de TPO foram sequenciados. No paciente foi identificada a duplicação em heterozigose GGCC no éxon 8 do gene TPO (c.1186_1187insGGCC). Nenhuma outra mutação foi localizada nos genes TPO, incluindo o promotor, DUOX2 ou DUOXA2. Descrevemos paciente com grave defeito de organificação de iodeto, provocando HC severo com bócio, em consequência de uma única mutação monoalélica no gene TPO. A expressão monoalélica no tecido tireoideano explicaria a associação de uma doen ça autossômica recessiva com uma única mutação monoalélica. Arq Bras Endocrinol Metab. 2010;54(8):732-7

Thyroid Peroxidase Gene Mutation in Patients with Congenital Hypothyroidism in Isfahan, Iran

“…Some studies have reported that homozygous and compound heterozygous TPO gene mutations are more frequently seen among dyshormonogenic CH patients with TIOD [32, 34]. It is suggested that low frequency of TPO gene mutations in our studied population may be due to the fact that most of them were dyshormonogenic CH patients with PIOD, which should be investigated in future studies.…”

“…The mutation of c.2669G > A (NM_000547.5) has been reported by Avbelj et al in Slovakia, and thereafter it was not reported in other studies [17]. Mutation of exon 15 has been reported by Neves et al in Brazil, but it was c.2630T > C mutation [32]. …”

Genetic analysis of thyroid peroxidase (<i>TPO</i>) gene in patients whose hypothyroidism was found in adulthood in West Bengal, India

“…Genetic analysis of TPO gene in both case and control, showed six single nucleotide changes, which include three synonymous (Ala576Ala: c.1728G>A: rs78406347 [21,22], Asp666Asp: c.1998C>T: rs1126797 [21][22][23][24][25] and Pro715Pro: c.2145C>T: rs732608 [21,23] ), one nonsynonymous (Thr725Pro: c.2173A>C: rs732609 [21][22][23] ) and two changes in intronic region ( IVS9+42T>C: rs6715129 [26] and IVS11+20G>A: rs10189329 [26] ). In addition two novel deletions [IVS12+144_+148delGGGGC and IVS12+144_+153delGGGGCGGGGC] in Intron-12 were observed in 2 patients (Table 2).…”

Mutations of the thyroid peroxidase gene in Chinese siblings with congenital goitrous hypothyroidism

“…Mutation analysis of the TPO gene in CGH patients has been reported in various ethnic populations (5,9,16). It is interesting to note that the compound TPO mutations were identified in the Chinese mainland, demonstrating the heterogeneous nature of TPO mutations among different ethnic groups.…”