一个透明纤维瘤病综合征家系的致病变异分析

目的探讨一对同患透明纤维瘤病综合征(hyaline fibromatosis syndrome,HFS)的孪生子的遗传学病因。方法回顾分析患儿的临床资料,并对其进行基因测序,用CLUSTALX软件分析候选变异位点氨基酸序列的保守性;用PolyPhen-2及MutationTaster软件对变异的致病性进行预测。结果患儿均发现全身皮肤多处结节、关节屈曲挛缩、皮肤色素沉着斑,其生长及智力发育均落后于同龄儿。基因检测发现其均携带ANTXR2基因c.1214G>A(p.G405D)、c.1074delT(p.P358fs)复合杂合变异,其中c.1214G>A(p.G405D)未见文献报道,功能预测为有害变异。随访发现二人生长及智力发育持续落后,牙龈及耳廓结节增大,弟弟耳廓结节破溃。结论c.1214G>A(p.G405D)及c.1074delT(p.P358fs)复合杂合变异可能为患儿的遗传学病因。上述发现为本病的诊断提供了依据。

Analysis of pathogenic variants in a Chinese pedigree affected with hyaline fibromatosis syndrome

Objective To explore the clinical characteristics and genetic basis for a pair of twins affected with hyaline fibromatosis syndrome(HFS).Methods Clinical data of the twins were retrospectively analyzed.High-throughput sequencing was carried out to detect potential pathogenic variants.CLUSTALX was employed to analyze cross-species conservation of the mutant amino acid.Impact of the mutations was predicted by using software including PolyPhen-2 and Mutation taster.Results The pair of twins have featured growth and intelligence retardation,and were found to carry compound heterozygous variants of the ANTXR2 gene including c.1214G>A and c.1074delT,among which c.1214G>A was unreported previously.Both variants were predicted to be pathogenic.In addition to growth and mental delay,the pair of twins also featured hyperplasia of the gum and soft tissue-like masses of the auricle.The younger brother had rupture of the auricle mass during follow-up.Conclusion The patients’condition may be attributed to the compound heterozygous variants of the ANTXR2 gene.Above finding has facilitated molecular diagnosis of the patients.