直系兄妹PNPLA6基因突变致Boucher-Neuhäuser综合征2例并文献复习

Boucher-Neuhäuser syndrome:a case of two siblings with two PNPLA6 mutations and literature review

目的探讨PNPLA6基因突变致Boucher-Neuhäuser综合征的临床特点和诊疗方法,并揭示基因检测对该遗传病诊断的重要性。方法回顾性分析两例直系兄妹因PNPLA6基因突变致患Boucher-Neuhäuser综合征,分析讨论该基因的结构和功能,以及因其突变导致的其他疾病临床特点。结果先证者和哥哥自幼身材矮小,眼底呈灰暗色,视网膜萎缩,可见骨细胞样色素沉着,黄斑周围有渗出,血管走行正常。全外显子组测序结果显示,先证者19号染色体上的PNPLA6基因出现了一对复合杂合突变。第一个突变位点是chr19:7621349,c.2990C>T(p.Ser997Leu,Exon 28),第二个突变位点是chr19:7623819,c.3367G>A(p.Gly1123Arg,Exon 31),哥哥在这两个位点上也均是杂合突变,其父母在这两个位点上均携带致病基因。结论根据病史、临床表现和基因检测结果,两兄妹被诊断为Boucher-Neuhäuser综合征。

Objective To explore and analyze the clinical features and diagnostic method of patients with Boucher-Neuhäuser syndrome caused by PNPLA6 gene mutation,and to reveal and make clear the importance of genetic testing method in the diagnosis of the genetic disease.Methods Two cases of Boucher-Neuhauser syndrome caused by PNPLA6 gene mutation were retrospectively analyzed.The structure and function of PNPLA6 gene as well as the clinical characteristics of other diseases caused by the mutation were analyzed and discussed.Results The proband and her brother were short stature since childhood.The fundus oculi was gray and dark with atrophied retina.There were some osteocytic pigmentation can be seen in the fundus oculi and the blood vessels'shape was normal.There were some exudations can be detected around the macula.Whole-exome sequencing results revealed a pair of compound heterozygous mutations in the PNPLA6 gene on the proband's chromosome 19.The first mutation was chr19:7621349,c.2990C>T(p.Ser997Leu,Exon 28).The second mutation was chr19:7623819,c.3367G>A(p.Gly1123Arg,Exon 31).The elder brother at these locus were also heterozygous mutation.Their parents were all carried disease-causing genes at these locus.Conclusion The two children were diagnosed with Boucher-Neuhäuser syndrome based on their medical history,clinical nanifestations and genetic testing results.