A Case of Congenital Central Hypothyroidism Caused by a Novel Variant (Gln1255Ter) in &lt;i&gt;IGSF1&lt;/i&gt; Gene

Türkkahraman, Doğa; Torun, Nimet Karataş; Randa, Nadide Cemre

doi:10.4274/jcrpe.galenos.2020.2020.0149

Cited by 4 publications

(4 citation statements)

References 12 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using current criteria for GHD, this was reported in 16% of children in IGSF1 deficiency ( 3 , 4 ), but in all cases GHD was transient. Similarly, a recently published Turkish patient with IGSF1 deficiency was treated with GH for two years, but during adolescence his GHD proved transient ( 21 ). Remarkably, in adult IGSF1 deficient patients IGF-1 levels are generally in the upper half or even above the reference range, with increased GH secretion and variable mild acromegalic features in late adulthood ( 3 , 4 , 6 ).…”

Section: Discussionmentioning

confidence: 96%

A Novel Pathogenic IGSF1 Variant in a Patient with GH and TSH Deficiency Diagnosed by High IGF-I Values at Transition to Adult Care

Kardelen¹,

Özturan²,

Poyrazoğlu³

et al. 2023

Jcrpe

View full text Add to dashboard Cite

IGSF1 deficiency is a rare X-linked condition characterized by central hypothyroidism and a wide variety of other clinical features with variable prevalence, including a delayed pubertal testosterone rise and growth spurt in the context of normal or accelerated testicular growth, and adult macroorchidism with relatively low serum testosterone concentrations. Other features include increased waist circumference, attention deficit, prolactin deficiency and transient partial growth hormone (GH) deficiency in childhood, contrasting with an increased GH secretion in adulthood. Patients with this disorder are not detected shortly after birth if neonatal screening programs are based on thyroid-stimulating hormone (TSH) concentrations. A 13.2-year-old male patient was referred to pediatric endocrinology for evaluation of short stature. He was born large for gestational age into a nonconsanguineous family. During work-up for short stature, deficiencies of TSH, prolactin and GH were detected, leading to treatment with levothyroxine and GH. At 16.9 years, GH treatment was stopped and during transition to adult care, his insulin-like growth factor 1 level was above the normal range. This prompted an analysis of IGSF1, in which a novel hemizygous variant causing a stop codon at c.3559C>T (p.Q1187*) was found, confirming the diagnosis of IGSF1 deficiency syndrome. In this report, we describe his clinical and hormonal characteristics at presentation and during long-term follow-up.

show abstract

Section: Discussionmentioning

confidence: 96%

A Novel Pathogenic IGSF1 Variant in a Patient with GH and TSH Deficiency Diagnosed by High IGF-I Values at Transition to Adult Care

Kardelen¹,

Özturan²,

Poyrazoğlu³

et al. 2023

Jcrpe

View full text Add to dashboard Cite

show abstract

“…A TRH test may be helpful in this context to differentiate hypothalamic and pituitary origins [13], although the value of TRH tests in pituitary assessments is debatable [13, 18], and as was the case here, variable results have been reported in IGSF1 deficiency [9, 19-27].…”

Section: Discussionmentioning

confidence: 99%

Congenital Central Hypothyroidism Caused by a Novel IGSF1 Variant Identified in a French Family

et al. 2022

View full text Add to dashboard Cite

Introduction Central congenital hypothyroidism (CCH) is a rare disorder that can be caused by X-linked mutations in the immunoglobulin superfamily member 1 (IGSF1) gene. Here, we describe four familial cases with a variable presentation due to a novel IGSF1 pathogenic variant. Case presentation In the index case, investigation at birth of suspected brain-lung-thyroid syndrome surprisingly revealed a central hypothyroidism. Next-generation sequencing (NGS) uncovered a novel IGSF1 pathogenic variant: a hemizygous single base duplication (G) resulting in a premature stop codon (NM_001555.4: c.2485dup, p.Ala829Glyfs*15). Further family investigations revealed missed neonatal CCH for the older brother who presented with prolonged jaundice (TSH 3.06 mUI/L, FT4 9.4 pmol/L, FT3 4.2 pmol/L). It also led to the diagnosis of CCH at 11 months of age for the younger brother, whose thyroid function was considered normal at birth. Neuropsychological evaluations showed no cognitive impairment for the eldest two brothers, but a slightly reduced processing-speed index compared with the other parameters for the oldest. Furthermore, a maternal uncle was diagnosed with biochemical CCH at 34 years of age, despite having few symptoms, and a complete work-up revealed prolactin deficiency and macroorchidism. Discussion This report of a rare case of neonatal CCH caused by IGSF1 deficiency highlights the importance of recognizing the neonatal signs of hypothyroidism to diagnose CCH as early as possible. Our results also show the importance of performing family genetic screening if a pathogenic variant is identified, to properly monitor carriers as CCH may develop over time. We suggest that these families should be followed up in the long-term to better understand the natural history of this syndrome and evaluate the need for hormone substitution.

show abstract

“…As thyroid hormones are critical for the development of the central nervous system, Individuals with CCH may result in developmental delay due to untreated neonatal hypothyroidism. 8 The underlying molecular basis of CCH is poorly understood, although the genetic studies have been reported in a few cases. [7][8][9][10][11][12] At present, genetic defects in only four genes (TSHB, TRHR, IGSF1 and the TBL1X) have been identified in patients with isolated CCH.…”

Section: Introductionmentioning

confidence: 99%

“…8 The underlying molecular basis of CCH is poorly understood, although the genetic studies have been reported in a few cases. [7][8][9][10][11][12] At present, genetic defects in only four genes (TSHB, TRHR, IGSF1 and the TBL1X) have been identified in patients with isolated CCH. 12 Here, we investigate the genetic mechanisms in seven patients with CCH by chromosomal microarray analysis (CMA) and whole-exome sequencing (WES).…”

Section: Introductionmentioning

confidence: 99%

Genetic Basis of Congenital Central Hypothyroidism in Children: Expanding the Mutational Spectrum of POU1F1 and ATP6V0A4

Fu,

Luo,

et al. 2023

IJGM

View full text Add to dashboard Cite

Congenital central hypothyroidism (CCH) is a rare disorder poorly described in childhood and adolescence. The current knowledge on the genetic bases of CCH is scarce. The purpose of this study was to analyze the clinical characteristics and molecular genetic basis of CCH in children. Methods: We conducted a thorough evaluation of the clinical features in children diagnosed with CCH. Genomic DNA was extracted from peripheral blood of both children and their parents, and chromosomal microarray analysis and whole-exome sequencing were performed. Candidates for single nucleotide variants were validated using Sanger sequencing and were classified according to the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines. Results: Two cases with likely pathogenic variants were detected by whole-exome sequencing. Individual 1 carried a novel homozygous ATP6V0A4 c.1418C>T (p.Ser473Phe) variant and a novel heterozygous POU1F1 c.416G>A. (p.Arg139Gln) variant. Individual 2 had a novel homozygous POU1F1 c.212C>T (p.Ala71Val) variant. The chromosomal microarray detected the presence of a 24 Mb heterozygous deletion (LOH: loss of heterozygosity) in the p12.1p13.13 region of chromosome 2 in individual 3, and the copy number variant was unknown of clinical significance. Conclusion:Our study employed chromosomal microarray and whole-exome sequencing to investigate central hypothyroidism in seven children, leading to the detection of genetic anomalies in three individuals. The identification of novel variants has contributed to the expanded genetic spectrum of POU1F1 and ATP6V0A4 associated with pediatric central hypothyroidism.

show abstract

A Case of Congenital Central Hypothyroidism Caused by a Novel Variant (Gln1255Ter) in <i>IGSF1</i> Gene

Cited by 4 publications

References 12 publications

A Novel Pathogenic IGSF1 Variant in a Patient with GH and TSH Deficiency Diagnosed by High IGF-I Values at Transition to Adult Care

A Novel Pathogenic IGSF1 Variant in a Patient with GH and TSH Deficiency Diagnosed by High IGF-I Values at Transition to Adult Care

Congenital Central Hypothyroidism Caused by a Novel IGSF1 Variant Identified in a French Family

Genetic Basis of Congenital Central Hypothyroidism in Children: Expanding the Mutational Spectrum of POU1F1 and ATP6V0A4

Contact Info

Product

Resources

About