A syndromic extreme insulin resistance caused by biallelic POC1A mutations in exon 10
A syndromic extreme insulin resistance caused by biallelic POC1A mutations in exon 10
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DOI：
10.1530/eje-17-0431
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发表时间：
2017-11-01
影响因子：
5.8
通讯作者：
Brusco, Alfredo
中科院分区：
文献类型：
--
作者：
Giorgio, Elisa;Rubino, Elisa;Brusco, Alfredo
POC1A编码一种在中心粒组装和稳定性以及纤毛发生中起作用的蛋白质。影响POC1A的双等位基因功能缺失突变导致SOFT综合征，这是一种以身材矮小、甲关节发育不良、面部畸形和毛少为特征的超罕见疾病。通过外显子组测序，我们在一个表现为身材矮小、面部多毛、脱发、血脂异常和极度胰岛素抵抗的患者中发现了一个纯合子移码突变（c.1047_1048dupC; p.G337Rfs*25）。截断变异体影响外显子10，由于转录物的替代处理，它仅保留在三个poc1a成熟rna中的两个中。SOFT综合征的临床差异支持了影响外显子10的POC1A突变与一种独特疾病相关的假设，证实了先前基于类似病例的假设。此外，该报告还提供了一个额外的遗传条件的例子，由于不同的转录处理而呈现临床异质性。总之，在极度胰岛素抵抗和身材矮小的患者中，应考虑到POC1A外显子10的突变。
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.