Identification of SOFT syndrome caused by a pathogenic homozygous splicing variant of POC1A: a case report.
Identification of SOFT syndrome caused by a pathogenic homozygous splicing variant of POC1A: a case report.
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由 POC1A 致病性纯合剪接变异引起的 SOFT 综合征的鉴定：病例报告
DOI：
10.1186/s12920-021-01055-1
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发表时间：
2021-08-21
影响因子：
2.7
通讯作者：
Yao R
中科院分区：
文献类型：
--
作者：
Li G;Chang G;Wang C;Yu T;Li N;Huang X;Wang X;Wang J;Wang J;Yao R
背景
POC1A的致病性变异导致SOFT综合征和变异POC1A相关（vPOC1A）综合征。SOFT综合征是一种罕见的原发性侏儒症，其特征为身材矮小、甲发育不良、面部畸形和发育不良。SOFT综合征与vPOC1A综合征的主要临床差异包括血脂异常伴胰岛素抵抗和黑棘皮病。据我们所知，这是第一个报告的SOFT综合征患者诊断为纯合剪接变异体，这可能有助于扩大我们的理解的基因型和表型信息的疾病。
个案列报
我们报告了一个7岁的男孩与软综合征。患者身材矮小，面部特征对称，包括前额突出，倒三角脸，内眦赘皮，小牙齿和大耳朵。实验室检查显示轻度胰岛素抵抗。全外显子组测序（WES）鉴定出患者POC1A基因中的纯合剪接变体（c.981+1GA），桑格测序证实其遗传自其杂合父母。剪接变体的进一步转录实验揭示了外显子9跳跃转录物的异常百分比。
结论
这是首次报道的病例软综合征患者与一个新的纯合剪接变异体和详细描绘的异常转录在先证者和携带者的变异在中国。本研究丰富了POC1A基因的突变谱，为进一步对SOFT综合征患者进行基因诊断和咨询提供了依据。
Background
Pathogenic variants in POC1A led to SOFT syndrome and variant POC1A-related (vPOC1A) syndrome. SOFT syndrome is a rare primordial dwarfism condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis.The main clinical differences between SOFT and vPOC1A syndrome include dyslipidemia with insulin resistance and acanthosis nigricans. To our knowledge, this is the first report of a SOFT syndrome patient diagnosed with a homozygous splicing variant, which could help to extend our understanding of the genotypic and phenotypic information of the disease.
Case presentation
We reported a seven-year-old boy with SOFT syndrome. The patient presented symmetrical short stature and facial features, including prominent forehead, inverted triangular face, epicanthal fold, small teeth and enlarged ears. Laboratory tests displayed mild insulin resistance. Whole-exome sequencing (WES) led to the identification of a homozygous splicing variant (c.981+1GA) in POC1A gene of the patient, which was inherited from his heterozygous parents confirmed by Sanger sequencing. Further transcriptional experiments of the splicing variant revealed aberrant percentage of exon 9 skipping transcripts.
Conclusions
This is the firstly reported case of a SOFT syndrome patient with a novel homozygous splicing variant and detailed delineation of the aberrant transcript in proband and carrier of the variant in Chinese. Our study enriched mutational spectrum of POC1A which could help in further genetic diagnosis and counselling of SOFT syndrome patients.
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POC1A的截断与矮小的身材和极端胰岛素抵抗有关。
影响因子：
3.5
作者：
Chen JH;Segni M;Payne F;Huang-Doran I;Sleigh A;Adams C;UK10K Consortium;Savage DB;O'Rahilly S;Semple RK;Barroso I
通讯作者：
Barroso I
影响因子：
3.3
作者：
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通讯作者：
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作者：
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Faivre, Laurence
影响因子：
5.8
作者：
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通讯作者：
Brusco, Alfredo
影响因子：
3.5
作者：
Majore, Silvia;Agolini, Emanuele;Grammatico, Paola
通讯作者：
Grammatico, Paola