Detection of Novel Gene Variants Associated with Congenital Hypothyroidism in a Finnish Patient Cohort.
Detection of Novel Gene Variants Associated with Congenital Hypothyroidism in a Finnish Patient Cohort.
复制标题
DOI：
10.1089/thy.2016.0016
复制
发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Kero J
中科院分区：
文献类型：
--
作者：
Löf C;Patyra K;Kuulasmaa T;Vangipurapu J;Undeutsch H;Jaeschke H;Pajunen T;Kero A;Krude H;Biebermann H;Kleinau G;Kühnen P;Rantakari K;Miettinen P;Kirjavainen T;Pursiheimo JP;Mustila T;Jääskeläinen J;Ojaniemi M;Toppari J;Ignatius J;Laakso M;Kero J
背景：先天性甲状腺功能减退症（CH）是指出生时缺乏甲状腺激素。至少有15种不同基因的突变与这种疾病有关。虽然高达20%的CH病例是遗传性的，但大多数病例是散发的，病因不明。除了单基因的遗传模式，多基因机制已被建议在CH中发挥作用。CH的遗传学至今尚未在芬兰进行研究。因此，多基因测序的CH候选基因进行了芬兰患者队列与家族性和散发性CH。方法：有针对性的下一代测序（NGS）面板，涵盖了主要CH基因的所有外显子，适用于15例散发性和11个指数例家族性CH。结果：在家族性病例中，6个致病性突变被发现在TPO，PAX 8和TSHR基因。此外，从散发病例中鉴定出致病性NKX2.1和TG突变，以及TG、NKX2.5、SLC 26 A4和DUOX 2基因中可能的致病性变体。所有鉴定的新型致病性突变均通过Sanger测序进行确认，并在计算机模拟和/或体外进行表征。结论：总之，CH面板提供了一个有效的，成本效益高，多基因的筛查工具，已知的和新的CH基因突变。因此，它可能是一个有用的方法，以准确地确定遗传病因的功能障碍，家族性或综合征形式的CH。
Background: Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH. Methods: A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH. Results: Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro. Conclusion: In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH.
登录
查看更多内容
DOI：
10.1155/2010/940980
发表时间：
2010
期刊：
International journal of pediatric endocrinology
影响因子：
--
作者：
Reddy PA;Rajagopal G;Harinarayan CV;Vanaja V;Rajasekhar D;Suresh V;Sachan A
通讯作者：
Sachan A
影响因子：
6.6
作者：
Nagashima, T;Murakami, M;Morikawa, A
通讯作者：
Morikawa, A
影响因子：
5.8
作者：
Labadi, Arpad;Grassi, Elisa Stellaria;Persani, Luca
通讯作者：
Persani, Luca
影响因子：
15.9
作者：
ABRAMOWICZ, MJ;TARGOVNIK, HM;VASSART, G
通讯作者：
VASSART, G
影响因子：
5.4
作者：
Liu, S. G.;Zhang, S. S.;Ma, X.
通讯作者：
Ma, X.