New Cases of Isolated Congenital Central Hypothyroidism Due to Homozygous Thyrotropin Beta Gene Mutations: A Pitfall to Neonatal Screening

Ramos, Helton Estrela; Labedan, Isabelle; Carré, Aurore; Castanet, Mireille; Guemas, Isabelle; Tron, Elodie; Madhi, Fouad; Delacourt, Christophe; Maciel, Rui M. B.; Polak, Michel

doi:10.1089/thy.2009.0462

Cited by 24 publications

(9 citation statements)

References 32 publications

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“…A previous report of IGSF1 mutations did not mention about the size of thyroid [10]. Compared to our patient, thyroid was hypoplasia in patients with TSHB mutations [16].Thus, TSH deficiency or inactivity typically results in a thyroid gland that is normally located, but hypoplastic. However, despite persistently undetectable TSH levels, normal 123 I thyroid uptake in two adult patients with goiter was reported [17].…”

Section: Resultscontrasting

confidence: 67%

A novel mutation of <i>IGSF1</i> in a Japanese patient of congenital central hypothyroidism without macroorchidism [Rapid Communication]

2013

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Abstract. Congenital central hypothyroidism (C-CH) is a rare disease known to be caused by mutations of the genes encoding TSH β or the TRH receptor gene, although the cause of the disease in a number of patients has not yet been clarified. Recently, mutations and deletions of the immunoglobulin superfamily member 1 (IGSF1) gene have been reported to be the cause of C-CH. Here we report a Japanese male patient with C-CH due to a novel IGSF1 mutation. He was detected by neonatal mass screening of simultaneous TSH and free T4 measurements and levothyroxine was initiated. At 6 years of age he underwent 123 I scintigraphy after levothyroxine treatment had been discontinued for one month and his thyroid and pituitary function were evaluated. Since TSH and PRL responses after TRH stimulation were low, his diagnosis of C-CH was confirmed. During follow up, whereas onset of his puberty was delayed, his secondary sex characterization completed at 17 years old. In this patient we analyzed IGSF1 and TRHR. As results, we identified a novel insertion mutation in IGSF1 (c.3528-3529insC), resulting in a premature stop codon (p.Pro1082Trpfs39X). In conclusion, we identified a novel mutation of IGSF1 in a Japanese male patient with C-CH.

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Section: Resultscontrasting

confidence: 67%

A novel mutation of <i>IGSF1</i> in a Japanese patient of congenital central hypothyroidism without macroorchidism [Rapid Communication]

2013

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“…If untreated with L-T4 within the first 6 weeks of life, these patients may develop cretinism (Bonomi et al, 2001;Miyai, 2007). In neonates, CeH can be identified only by screening programs based on concomitant TSH and total or free T 4 measurements on dried blood spot testing (Kempers et al, 2006;Baquedano et al, 2010;Nebesio et al, 2010;LaFranchi, 2010;Ramos et al, 2010;Adachi et al, 2012). CeH confirmation by serum free T 4 and abnormal TSH response to thyrotropin-releasing hormone (TRH) testing may reveal the risk of CPHDs and impending adrenal crisis.…”

Section: Inheritable Central Hypothyroidismmentioning

confidence: 99%

Uncertainties in endocrine substitution therapy for central endocrine insufficiencies

Persani

Bonomi

2014

Clinical Neuroendocrinology

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“…In this context, the p.S304R hinge variant does not seem to be functionally important, and the described dysgenetic phenotype would only be explained by the heterozygous p.R31C mutation, which was exclusively found in the propositus patient. The deleterious effect of PAX8 mutation has already been demonstrated (33). We can assume that the wearing 2 mutations on the PAX8 and TSHR synergize default size and functional thyroid.…”

Section: Discussionmentioning

confidence: 75%

Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion

Cerqueira¹,

Carré

Chevrier

et al. 2015

Journal of Pediatric Endocrinology and Metabolism

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We report the ocurrence of a novel nonsynonymous substitution in the HinR of the large N-terminal extracellular domain of the TSHR gene in a patient with thyroid hypoplasia. In contrast with four others in whom TSHR mutations of the hinge portion were previously identified, the p.S304R TSHR variation neither affected TSH binding nor cAMP pathway activation. This TSHR gene variant was documented in a CH patient, but the current data do not support its role in the clinical phenotype.

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New Cases of Isolated Congenital Central Hypothyroidism Due to Homozygous Thyrotropin Beta Gene Mutations: A Pitfall to Neonatal Screening

Abstract: The marked phenotypic variability in patients with the c.Q49X mutation suggests modulation by interacting genes and/or differences in the genetic background. TSHbeta gene mutations should be suspected in neonates with inappropriately low TSH levels.

Cited by 24 publications

References 32 publications

A novel mutation of <i>IGSF1</i> in a Japanese patient of congenital central hypothyroidism without macroorchidism [Rapid Communication]

A novel mutation of <i>IGSF1</i> in a Japanese patient of congenital central hypothyroidism without macroorchidism [Rapid Communication]

Uncertainties in endocrine substitution therapy for central endocrine insufficiencies

Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion

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