Pathogenic variants in components of the minor spliceosome have been associated with several human diseases. Recently, it was reported that biallelic RNPC3 variants lead to severe isolated growth hormone deficiency and pituitary hypoplasia. The RNPC3 gene codes for the U11/U12-65K protein, a component of the minor spliceosome. The minor spliceosome plays a role in the splicing of minor (U12-type) introns, which are present in ~700–800 genes in humans and represent about 0.35% of all introns. Here, we report a second family with biallelic RNPC3 variants in three siblings with a growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. These cases further confirm the association between biallelic RNPC3 variants and severe postnatal growth retardation due to growth hormone deficiency. Furthermore, these cases show that the phenotype of this minor spliceosome-related disease might be broader than previously described.

Original languageEnglish
Pages (from-to)1952-1956
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Issue number8
Early online date2020
Publication statusPublished - 1 Aug 2020


  • RNPC3
  • central congenital hypothyroidism
  • congenital cataract
  • developmental delay/intellectual deficiency
  • growth hormone deficiency
  • minor spliceosome

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