Molecular spectrum of TSHβ subunit gene defects in central hypothyroidism in the UK and Ireland
| العنوان: | Molecular spectrum of TSHβ subunit gene defects in central hypothyroidism in the UK and Ireland |
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| المؤلفون: | Nicholas, AK, Jaleel, S, Lyons, G, Schoenmakers, E, Dattani, MT, Crowne, E, Bernhard, B, Kirk, J, Roche, EF, Chatterjee, VK, Schoenmakers, N |
| المساهمون: | Schoenmakers, Erik [0000-0003-0674-8282], Chatterjee, Krishna [0000-0002-2654-8854], Schoenmakers, Nadia [0000-0002-0847-2884], Apollo - University of Cambridge Repository |
| المصدر: | Clinical Endocrinology |
| بيانات النشر: | John Wiley and Sons Inc., 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, Heterozygote, Delayed Diagnosis, Homozygote, Infant, Newborn, Original Articles, Sequence Analysis, DNA, Thyrotropin, beta Subunit, United Kingdom, Pedigree, Editor's Choice, Neonatal Screening, Hypothyroidism, Congenital Hypothyroidism, Humans, Original Article, Female, Ireland |
| الوصف: | Summary Objective Homozygous mutations in the TSH beta subunit gene (TSHB) result in severe, isolated, central congenital hypothyroidism (CCH). This entity evades diagnosis in TSH‐based congenital hypothyroidism (CH) screening programmes in the UK and Ireland. Accordingly, genetic diagnosis, enabling ascertainment of affected relatives in families, is critical for prompt diagnosis and treatment of the disorder. Design, Patients and Measurements Four cases of isolated TSH deficiency from three unrelated families in the UK and Ireland were investigated for mutations or deletions in TSHB. Haplotype analysis, to investigate a founder effect, was undertaken in cases with identical mutations (c.373delT). Results Two siblings in kindred 1 were homozygous for a previously described TSHB mutation (c.373delT). In kindreds 2 and 3, the affected individuals were compound heterozygous for TSHB c.373delT and either a 5·4‐kB TSHB deletion (kindred 2, c.1‐4389_417*195delinsCTCA) or a novel TSHB missense mutation (kindred 3, c.2T>C, p.Met1?). Neurodevelopmental retardation, following delayed diagnosis and treatment, was present in 3 cases. In contrast, the younger sibling in kindred 1 developed normally following genetic diagnosis and treatment from birth. Conclusions This study, including the identification of a second, novel, TSHB deletion, expands the molecular spectrum of TSHB defects and suggests that allele loss may be a commoner basis for TSH deficiency than previously suspected. Delayed diagnosis and treatment of profound central hypothyroidism in such cases result in neurodevelopmental retardation. Inclusion of thyroxine (T4) plus thyroxine‐binding globulin (TBG), or free thyroxine (FT4) in CH screening, together with genetic case ascertainment enabling earlier therapeutic intervention, could prevent such adverse sequelae. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1365-2265 0300-0664 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::5a9b7b8eb9a438c7e86cd79d8979c267 http://europepmc.org/articles/PMC5324561 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.pmid.dedup....5a9b7b8eb9a438c7e86cd79d8979c267 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652265 03000664 |
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