TY - JOUR
T1 - A syndromic extreme insulin resistance caused by biallelic POC1A mutations in exon 10
AU - Giorgio, Elisa
AU - Rubino, Elisa
AU - Bruselles, Alessandro
AU - Pizzi, Simone
AU - Rainero, Innocenzo
AU - Duca, Sergio
AU - Sirchia, Fabio
AU - Pasini, Barbara
AU - Tartaglia, Marco
AU - Brusco, Alfredo
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
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U2 - 10.1530/EJE-17-0431
DO - 10.1530/EJE-17-0431
M3 - Article
C2 - 28819016
AN - SCOPUS:85031005595
VL - 177
SP - K21-K27
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 5
ER -