A novel <scp>IGSF</scp>1 mutation in a large Irish kindred highlights the need for familial screening in the <scp>IGSF</scp>1 deficiency syndrome

Roche, Edna; McGowan, Anne; Koulouri, Olympia; Turgeon, Marc-Olivier; Nicholas, Adeline K.; Heffernan, Emmeline; El-Khairi, Ranna; Abid, Noina; Lyons, Greta; Halsall, David; Bonomi, Marco; Persani, Luca; Dattani, Mehul; Gurnell, Mark; Bernard, Daniel J.; Schoenmakers, Nadia

doi:10.1111/cen.13827

Cited by 21 publications

(21 citation statements)

References 32 publications

(69 reference statements)

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“…All but one of the reported mutations are located in the C-terminal domain of the protein and impair IGSF1 trafficking from the endoplasmic reticulum to the plasma membrane. There is no clear genotype-phenotype correlation, while variation in the extent of hypothyroidism or the other clinical features, even within families, has been reported (8,9). IGSF1 is expressed in thyrotrope cells of the anterior pituitary.…”

Section: Discussionmentioning

confidence: 99%

Hypoprolactinemia as a Clue to Diagnosis of Mild Central Hypothyroidism due to <i>IGSF1</i> Deficiency

Papadimitriou

Papadopoulou

Kleanthous

et al. 2020

Jcrpe

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Loss-of-function mutations of IGSF1 are an X-linked cause of central hypothyroidism (CeH) and hypoprolactinemia. A boy who is now 15.2 years old presented at the age of 7.69 years for evaluation of obesity. Previous thyroid function evaluation suggested CeH [FT4 0.6 ng/mL, thyroid-stimulating hormone (TSH) 2.2 mIU/L] but his physician took no action. At presentation he was clinically and biochemically euthyroid, prepubertal and obese. Serum prolactin (PRL) was undetectable. Biochemistry was normal except for mild hypercholesterolemia, total cholesterol 198 mg/dL. Subsequently FT4 and TSH levels fluctuated between 0.72-0.95 ng/dL (normal 0.8-2.0) and 1.94-5.77 mIU/L (normal 0.3-5.0), respectively. Sequencing of IGSF1 gene revealed a novel genetic change c.3805C>T in exon 19; substitution of amino acid Arginine at position 1269 with a premature «stop» codon resulting in an altered protein product. The patient additionally presented delayed adrenarche, low height velocity that resolved spontaneously and normal pubertal onset associated with increased FSH levels. At 14 years-of-age, while the patient was at Tanner stage 4, PRL levels became detectable, rising gradually to 2.3 ng/mL at last examination. Thyroxine replacement therapy resulted in decrease in total cholesterol 103 mg/dL. A high index of suspicion for the disorder is needed since several measurements of thyroid function may be required for CeH to be disclosed. The patient's normal FT4 levels and normal intelligence would have resulted in a missed diagnosis if the serum PRL levels had not been measured. This case highlights the importance of measuring PRL in a boy with low normal FT4 and normal TSH levels.

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Section: Discussionmentioning

confidence: 99%

Hypoprolactinemia as a Clue to Diagnosis of Mild Central Hypothyroidism due to <i>IGSF1</i> Deficiency

Papadimitriou

Papadopoulou

Kleanthous

et al. 2020

Jcrpe

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“…For instance, loss-of-function mutations in IGSF1 result in an X-linked syndrome of central hypothyroidism and testicular enlargement. IGSF1 mutations in male patients lead to a late increase in testosterone levels ( Howard et al, 2016 ; Roche et al, 2018 ; Sun et al, 2012 ). Significantly prolonged OS was observed in pediatric patients with mixed-lineage leukemia-rearranged acute monoblastic leukemia with t(9; 11) (p22; q23) and high IGSF4 expression than in patients with low IGSF4 expression ( Kuipers et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin superfamily member 10 is a novel prognostic biomarker for breast cancer

Wang

Dai

et al. 2020

PeerJ

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Background Immunoglobulin superfamily member 10 (IGSF10) is a member of the immunoglobulin superfamily that is expressed at high levels in both the gallbladder and ovary. Currently, the role and possible mechanism of IGSF10 in breast cancer remain unclear. Method By applying real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), the expression of IGSF10 in breast cancer cells and tissues was detected. We collected the clinical information from 700 patients with breast cancer in The Cancer Genome Atlas (TCGA), and analyzed the relationship between IGSF10 expression and the clinicopathological features and survival outcomes of these patients. The potential mechanisms and pathways associated with IGSF10 in breast cancer were explored by performing a gene set enrichment analysis (GSEA). Results According to TCGA data, qRT-PCR and IHC experiments, levels of the IGSF10 mRNA and protein were significantly decreased in breast cancer tissues. IGSF10 expression was significantly correlated with age, tumor size, and tumor stage. Moreover, shorter overall survival (OS) and relapse-free survival (RFS) correlated with lower IGSF10 expression, according to the survival analysis. The multivariate analysis identified that IGSF10 as an independent prognostic factor for the OS (hazard ratio (HR) = 1.793, 95% confidence interval (CI) [1.141–2.815], P = 0.011) and RFS (HR = 2.298, 95% CI [1.317–4.010], P = 0.003) of patients with breast cancer. Based on the GSEA, IGSF10 was involved in DNA repair, cell cycle, and glycolysis. IGSF10 was also associated with the PI3K/Akt/mTOR and mTORC1 signaling pathways. Conclusions This study revealed a clear relationship between IGSF10 expression and the tumorigenesis of breast cancer for the first time. Therefore, further studies are needed to understand the mechanism of IGSF10 in breast cancer.

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“…The multivariate analysis identified IGSF10 as an independent prognostic factor for patients with breast cancer. (Howard et al, 2016;Roche et al, 2018;Sun et al, 2012). Significantly prolonged OS was observed in pediatric patients with mixed-lineage leukemia-rearranged acute monoblastic…”

Section: Zhaomentioning

confidence: 99%

Peer Review #3 of "Immunoglobulin superfamily member 10 is a novel prognostic biomarker for breast cancer (v0.3)"

Zhang¹

2020

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Background. Immunoglobulin superfamily member 10 (IGSF10) is a member of the immunoglobulin superfamily that is expressed at high levels in both the gallbladder and ovary. Currently, the role and possible mechanism of IGSF10 in breast cancer remain unclear. Method. By applying real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), the expression of IGSF10 in breast cancer cells and tissues was detected. We collected the clinical information from 700 patients with breast cancer in The Cancer Genome Atlas (TCGA), and analyzed the relationship between IGSF10 expression and the clinicopathological features and survival outcomes of these patients. The potential mechanisms and pathways associated with IGSF10 in breast cancer were explored by performing a gene set enrichment analysis (GSEA). Results. According to TCGA data, qRT-PCR and IHC experiments, levels of the IGSF10 mRNA and protein were significantly decreased in breast cancer tissues. IGSF10 expression was significantly correlated with age, tumor size, and tumor stage. Moreover, shorter overall survival (OS) and relapse-free survival (RFS) correlated with lower IGSF10 expression, according to the survival analysis. The multivariate analysis identified that IGSF10 as an independent prognostic factor for the OS (hazard ratio (HR)=1.793, 95% confidence interval (CI): 1.141-2.815, P=0.011) and RFS (HR=2.298, 95% CI: 1.317-4.010, P=0.003) of patients with breast cancer. Based on the GSEA, IGSF10 was involved in DNA repair, cell cycle, and glycolysis. IGSF10 was also associated with the PI3K/Akt/mTOR and mTORC1 signaling pathways. Conclusions. This study revealed a clear relationship between IGSF10 expression and the tumorigenesis of breast cancer for the first time. Therefore, further studies are needed to understand the mechanism of IGSF10 in breast cancer.

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A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome

Cited by 21 publications

References 32 publications

Hypoprolactinemia as a Clue to Diagnosis of Mild Central Hypothyroidism due to <i>IGSF1</i> Deficiency

Hypoprolactinemia as a Clue to Diagnosis of Mild Central Hypothyroidism due to <i>IGSF1</i> Deficiency

Immunoglobulin superfamily member 10 is a novel prognostic biomarker for breast cancer

Peer Review #3 of "Immunoglobulin superfamily member 10 is a novel prognostic biomarker for breast cancer (v0.3)"

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