Clinical presentation and molecular characterization of a novel patient with variant POC1A‐related syndrome,Clinical Genetics

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Clinical presentation and molecular characterization of a novel patient with variant POC1A‐related syndrome
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-12-28 , DOI: 10.1111/cge.13911
Silvia Majore ₁ , Emanuele Agolini ₂ , Lucia Micale ₃ , Giulia Pascolini ₁ , Paolo Zuppi ₄ , Dario Cocciadiferro ₂ , Silvia Morlino ₁ , Matteo Mattiuzzo ₂ , Michele Valiante ₁ , Marco Castori ₃ , Antonio Novelli ₂ , Paola Grammatico ₁

Affiliation

Biallelic pathogenic variants in POC1A result in SOFT (Short‐stature, Onychodysplasia, Facial‐dysmorphism, and hypoTrichosis) and variant POC1A‐related (vPOC1A) syndromes. The latter, nowadays described in only two unrelated subjects, is associated with a restricted spectrum of variants falling in exon 10, which is naturally skipped in a specific POC1A mRNA. The synthesis of an amount of a POC1A isoform from this transcript in individuals with vPOC1A syndrome has been believed as the likely explanation for such a genotype–phenotype correlation. Here, we illustrate the clinical and molecular findings in a woman who resulted to be compound heterozygous for a recurrent frameshift variant in exon 10 and a novel variant in exon 9 of POC1A. Phenotypic characteristics of this woman included severe hyperinsulinemic dyslipidemia, acanthosis nigricans, moderate growth restriction, and dysmorphisms. These manifestations overlap the clinical features of the two previously published individuals with vPOC1A syndrome. RT‐PCR analysis on peripheral blood and subsequent sequencing of the obtained amplicons demonstrated a variety of POC1A alternative transcripts that resulted to be expressed in the proband, in the healthy mother, and in controls. We illustrate the possible consequences of the two POC1A identified variants in an attempt to explain pleiotropy in vPOC1A syndrome.

中文翻译：

一名新的变异 POC1A 相关综合征患者的临床表现和分子特征

在双等位基因致病突变POC1A结果在SOFT（小号园艺-身材，ö nychodysplasia，˚F acial-异形和低Ť richosis）和变体POC1A相关（vPOC1A）综合征。后者，现在仅在两个不相关的主题中描述，与落在外显子 10 中的变体的有限谱相关，在特定的POC1A 中自然跳过mRNA。在患有 vPOC1A 综合征的个体中，从该转录物合成一定量的 POC1A 同种型被认为是这种基因型 - 表型相关性的可能解释。在这里，我们说明了一名女性的临床和分子发现，该女性因POC1A的外显子 10 的复发性移码变异和外显子 9 的新变异而成为复合杂合子。该女性的表型特征包括严重的高胰岛素血脂异常、黑棘皮病、中度生长受限和畸形。这些表现与先前发表的两个 vPOC1A 综合征患者的临床特征重叠。外周血的 RT-PCR 分析和随后对获得的扩增子的测序证明了多种POC1A导致在先证者、健康母亲和对照中表达的替代转录物。我们说明了两种POC1A鉴定变体的可能后果，试图解释 vPOC1A 综合征中的多效性。

更新日期：2021-03-05

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