Two siblings with congenital central hypothyroidism caused by a novel mutation in the IGSF1 gene

Abstract. Genetic defects in the immunoglobulin superfamily member 1(IGSF1) protein are the cause of congenital central hypothyroidism (C-CH). Here we report two Japanese siblings with C-CH due to a novel IGSF1 mutation. The youngest brother showed a failure to thrive, hypothermia, and neonatal icterus six days after birth. Further endocrine evaluations led to the diagnosis of C-CH. In addition, PRL deficiency was later detected. In contrast, the elder brother did not show symptoms of severe hypothyroidism during the neonatal period, but he had been followed up by doctors due to psychomotor developmental delays since the age of 1 yr. At the age of 3 yr, he had low thyroxine and PRL levels and was also diagnosed with C-CH. Because of the C-CH and PRL deficiency, an IGSF1 deficiency was suspected. Sequence analysis of the IGSF1 gene identified a novel hemizygous mutation of p.Trp1173GlyfsTer8 (NM_001170961.1:c.3517del) in both siblings. In conclusion, the phenotypic severity of C-CH is different, even in siblings. Importantly, an IGSF1 deficiency may result in severe hypothyroidism during the neonatal period.

• Publication year

  2018

• Venue

  Clinical Pediatric Endocrinology

• Publication date

  2018-04-13

• Fields of study

  Medicine

• Identifiers
  DOI 10.1297/cpe.27.95PMID 29662269PMCID 5897585
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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