Identification of Oliver-McFarlane syndrome caused by novel compound heterozygous variants of PNPLA6
Identification of Oliver-McFarlane syndrome caused by novel compound heterozygous variants of PNPLA6
复制标题
鉴定由 PNPLA6 的新型复合杂合变体引起的 Oliver-McFarlane 综合征
DOI：
10.1016/j.gene.2020.145027
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发表时间：
2020-11-30
期刊：
影响因子：
3.5
通讯作者：
Sun, Yan
中科院分区：
文献类型：
--
作者：
Liu, Fan;Ji, Yiming;Sun, Yan
目的：Oliver-McFarlane综合征（OMCS）是一种由PNPLA 6突变引起的常染色体隐性遗传疾病，可导致智力障碍和严重的身材矮小。为了更好地了解PNPLA 6相关疾病的基因型-表型相关性，我们报告了第14例OMCS病例，并对所有OMCS病例进行了总结。我们收集了临床生化数据和脑MRI数据，并使用全外显子基因检测和分析工具来评估变体的致病性，包括PolyPhen-2和Mutation Taster，结果：该患者表现为毛发肥大和多种垂体激素缺乏。脑MRI显示小垂体和双侧脑室旁白质软化。在先证者中检测到PNPLA 6基因的新变异（c.1491G > T和c.3367G > A），并通过直接测序进行验证。Gln 497和Gly 1123的氨基酸残基被预测为破坏和破坏蛋白质的三维蛋白质结构。在追踪中，这位病人在一岁零十个月时，既不能走路，也不能抬头，也不能说一句话。此外，在任何已报道的等位基因变体中均没有明显的热点突变。有趣的是，大多数突变位于磷脂酯酶结构域，这是负责酯酶activity.Conclusions：我们确定了两个新的PNPLA 6基因的变体在OMCS患者，这将有助于更好地了解PNPLA 6的功能和基因型-表型相关性PNPLA 6相关疾病。
Objectives: Oliver-McFarlane syndrome (OMCS) is an autosomal recessive inherited disease resulting from PNPLA6 mutations that results in intellectual impairment and profound short stature. To obtain a better understanding of the genotype-phenotype correlations for PNPLA6-related disorders, we reported the 14th OMCS case and summarized all the reported cases of OMCS.Methods: We collected clinical biochemical and data and brain MRI data and used whole-exon gene detection and analysis tools to evaluate the pathogenicity of the variants, including PolyPhen-2 and Mutation Taster, and we also generated three-dimensional protein structures and visualized the effects of altered residues with I-TASSER and PyMOL Viewer software.Results: The patient presented with trichomegaly and multiple pituitary hormone deficiencies. Brain MRI showed small pituitary and bilateral paraventricular leukomalacia. Novel variants (c.1491G > T and c.3367G > A) in the PNPLA6 gene were detected in the proband and verified by direct sequencing. Amino acid residues of Gln497 and Gly1123 are predicted to be damaging and destroy the three-dimensional protein structures of the protein. In follow-up, this patient could neither walk nor hold his head erect and had not spoken one word at the age of one year and ten months. Moreover, there is no obvious hot spot mutation in any of the reported allelic variants. Interestingly, the majority of mutations are located in the phospholipid esterase domain, which is responsible for esterase activity.Conclusions: We identified two novel variants of the PNPLA6 gene in an OMCS patient, which will help to better understand the function of PNPLA6 and genotype-phenotype correlations for PNPLA6-related disorders.