A syndromic extreme insulin resistance caused by biallelic POC1A mutations in exon 10

E. Giorgio, E. Rubino, A. Bruselles, S. Pizzi, I. Rainero, S. Duca, F. Sirchia, B. Pasini, M. Tartaglia, A. Brusco

Research output: Contribution to journalArticlepeer-review


POC1A encodes a protein with a role in centriole assembly and stability, and in ciliogenesis. Biallelic loss-of-function mutations affecting POC1A cause SOFT syndrome, an ultra-rare condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis. Using exome sequencing, we identified a homozygous frameshift mutation (c.1047_1048dupC; p.G337Rfs*25) in a patient presenting with short stature, facial hirsutism, alopecia, dyslipidemia and extreme insulin resistance. The truncating variant affected exon 10, which is retained in only two of the three POC1A-mature RNAs, due to alternative processing of the transcript. Clinical discrepancies with SOFT syndrome support the hypothesis that POC1A mutations affecting exon 10 are associated with a distinct condition, corroborating a previous hypothesis based on a similar case. Furthermore, this report provides an additional example of a genetic condition presenting with clinical heterogeneity due to alternative transcript processing. In conclusion, POC1A mutations in exon 10 should be taken into account in patients with extreme insulin resistance and short stature. © 2017 European Society of Endocrinology.
Original languageEnglish
Pages (from-to)K21-K27
JournalEuropean Journal of Endocrinology
Issue number5
Publication statusPublished - 2017


  • insulin
  • insulin aspart
  • insulin detemir
  • metformin
  • proteome
  • proteome of centriole 1a
  • unclassified drug
  • POC1A protein, human
  • protein
  • acanthosis nigricans
  • adult
  • allele
  • alopecia
  • amenorrhea
  • Article
  • body mass
  • carpal tunnel syndrome
  • case report
  • clinical article
  • clinical examination
  • diabetes mellitus
  • dyslipidemia
  • evening dosage
  • exon
  • face dysmorphia
  • female
  • frameshift mutation
  • hirsutism
  • human
  • hypercholesterolemia
  • hyperinsulinemia
  • hyperprolactinemia
  • hypertriglyceridemia
  • hyperuricemia
  • hypotrichosis
  • insulin blood level
  • insulin resistance
  • knee osteoarthritis
  • low level laser therapy
  • low set ear
  • menarche
  • menstrual cycle
  • metatarsal bone
  • micrognathia
  • nail dystrophy
  • nail hypoplasia
  • nasolabial fold
  • nuclear magnetic resonance imaging
  • oral glucose tolerance test
  • osteosclerosis
  • polyneuropathy
  • prematurity
  • priority journal
  • short stature
  • vertebra body
  • whole exome sequencing
  • Abnormalities, Multiple
  • genetics
  • mutation
  • pleiotropy
  • syndrome
  • Adult
  • Alleles
  • Exons
  • Female
  • Genetic Pleiotropy
  • Humans
  • Insulin Resistance
  • Mutation
  • Proteins
  • Syndrome


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