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.

中文翻译：

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鉴定由PNPLA6的新型复合杂合变体引起的Oliver-McFarlane综合征。

目标

Oliver-McFarlane综合征（OMCS）是由PNPLA6突变引起的常染色体隐性遗传疾病，导致智力受损和身材矮小。为了更好地了解PNPLA6相关疾病的基因型与表型的相关性，我们报道了第14例OMCS病例并总结了所有报道的OMCS病例。

方法

我们收集了临床生化和数据以及脑MRI数据，并使用了全外显子基因检测和分析工具来评估包括PolyPhen-2和Mutation Taster在内的变异体的致病性，并且还生成了三维蛋白质结构并可视化了其效果。使用I-TASSER和PyMOL Viewer软件改变残基。

结果

该患者表现出毛滴虫和多种垂体激素缺乏症。脑MRI显示垂体和双侧小脑室白细胞减少。在先证者中检测到PNPLA6基因中的新变异（c.1491G> T和c.3367G> A），并通过直接测序进行验证。Gln497和Gly1123的氨基酸残基预计会破坏并破坏蛋白质的三维蛋白质结构。在随访中，该患者既不能走路也不能直立头部，并且在一年零十个月的时候没有说一句话。而且，在任何报道的等位基因变体中都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中，该结构负责酯酶活性。

结论

我们在OMCS患者中鉴定了PNPLA6基因的两个新变体，这将有助于更好地了解PNPLA6的功能以及与PNPLA6相关的疾病的基因型与表型的相关性。