FLNA基因变异致额骨干骺端发育不良1型一例

目的探讨FLNA基因变异所致额骨干骺端发育不良1型(frontometaphyseal dysplasia 1,FMD1)的临床及遗传学特点。方法分析患儿的临床表型,应用全外显子测序技术对先证者进行致病基因变异筛查,用Sanger测序法对其父母进行验证。结果先证者男性,2岁9个月,表现为特殊面容:眉弓轻度突出、眼睑下斜、眼距宽,骨骼畸形:双下肢弯曲、右膝外翻、左膝内翻、双手食指及中指轻度畸形、小指屈曲挛缩,左肘关节活动受限。基因测序发现患儿FLNA基因存在错义变异c.3527G>A,p.Gly1176Glu(半合子),父母均未携带该变异。结论FLNA基因变异引起的FMD1在婴幼儿时期即可出现关节挛缩、长骨发育不良,并随年龄增长进展,需要长期随访治疗。本例患儿FLNA基因变异位点尚未见文献报道。

Frontometaphyseal dysplasia 1 caused by variant of FLNA gene in a case

Objective To explore the clinical and genetic characteristics of a child with frontometaphyseal dysplasia 1(FMD1)due to variant of FLNA gene.Methods Clinical phenotype of the patient was analyzed.Whole exome sequencing(WES)was carried out to detect pathogenic genetic variants.Sanger sequencing was used to verified the result in his parents.Results The 2-year-and-9-month-old boy presented with facial dysmorphism(supraorbital hyperostosis,down-slanting palpebral fissure and ocular hypertelorism),skeletal deformities(bowed lower limbs,right genu valgum,left genu varus,slight deformity of index and middle fingers,and flexion contracture of little fingers).He also had limited left elbow movement.High-throughput sequencing revealed that he has carried a de novo heterogeneous c.3527G>A(p.Gly1176Glu)missense variant of the FLNA gene.The same variant was found in neither parent.Conclusion The clinical manifestations of FMD1 such as joint contracture and bone dysplasia can occur in infancy and deteriorate with age,and require long-term follow-up and treatment.Above finding has expanded the spectrum of FLNA gene variants.