مورد إلكتروني
Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations: molecular and in silico studies.
| العنوان: | Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations: molecular and in silico studies. |
|---|---|
| المصدر: | The Journal of clinical endocrinology and metabolism, 93 (2 |
| بيانات النشر: | 2008-02 |
| تفاصيل مُضافة: | Deladoëy, Johnny Pfarr, Nicole Vuissoz, Jean-Marc Parma, Jasmine Vassart, Gilbert Biesterfeld, Stefan Pohlenz, Joachim Van Vliet, G. |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | CONTEXT AND OBJECTIVE: Most cases of goitrous congenital hypothyroidism (CH) from thyroid dyshormonogenesis 1) follow a recessive mode of inheritance and 2) are due to mutations in the thyroid peroxidase gene (TPO). We report the genetic mechanism underlying the apparently dominant inheritance of goitrous CH in a nonconsanguineous family of French Canadian origin. DESIGN, SETTING, AND PARTICIPANTS: Two brothers identified by newborn TSH screening had severe hypothyroidism and a goiter with increased (99m)Tc uptake. The mother was euthyroid, but the father and two paternal uncles had also been diagnosed with goitrous CH. After having excluded PAX8 gene mutations, we hypothesized that the underlying defect could be TPO mutations. RESULTS: Both compound heterozygous siblings had inherited a mutant TPO allele carried by their mother (c.1496delC; p.Pro499Argfs2X), and from their father, one brother had inherited a missense mutation (c.1978C-->G; p.Gln660Glu) and the other an insertion (c.1955insT; p.Phe653Valfs15X). The thyroid gland of one uncle who is a compound heterozygote for TPO mutations (p.Phe653Valfs15X/p.Gln660Glu) was removed because of concurrent multiple endocrine neoplasia type 2A. Immunohistochemistry revealed normal TPO staining, implying that Gln660Glu TPO is expressed properly. Modeling of this mutant in silico suggests that its three-dimensional structure is conserved, whereas the electrostatic binding energy between the Gln660Glu TPO and its heme group becomes repulsive. CONCLUSION: We report a pedigree presenting with pseudodominant goitrous CH due to segregation of three different TPO mutations. Although goitrous CH generally follows a recessive mode of inheritance, the high frequency of TPO mutations carriers may lead to pseudodominant inheritance. Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| مصطلحات الفهرس: | Sciences bio-médicales et agricoles, Amino Acid Sequence, Base Sequence, Congenital Hypothyroidism -- enzymology, Congenital Hypothyroidism -- genetics, DNA -- genetics, Female, Goiter -- enzymology, Goiter -- genetics, Humans, Infant, Newborn, Iodide Peroxidase -- chemistry, Iodide Peroxidase -- genetics, Male, Models, Molecular, Molecular Sequence Data, Mutation, Pedigree, Polymerase Chain Reaction, Sequence Alignment, Static Electricity, Surface Properties, info:eu-repo/semantics/article, info:ulb-repo/semantics/articlePeerReview, info:ulb-repo/semantics/openurl/article |
| URL: | |
| الإتاحة: | Open access content. Open access content 1 full-text file(s): info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | 1 full-text file(s): application/pdf English |
| أرقام أخرى: | EQY oai:dipot.ulb.ac.be:2013/52416 uri/info:doi/10.1210/jc.2007-2276 uri/info:pii/jc.2007-2276 uri/info:pmid/18029453 uri/info:scp/39049085332 764587279 |
| المصدر المساهم: | UNIVERSITE LIBRE DE BRUXELLES From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.ocn764587279 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |