儿童Alport综合征合并GJB2基因突变1例分析并文献复习

目的 探讨Alport综合征合并GJB2基因突变导致儿童耳聋的临床特点及基因型分析。方法 回顾性分析西安市儿童医院肾脏科收治的1例儿童Alport综合征患儿的临床资料及基因检测结果。结果 患儿女,3岁8月,以血尿蛋白尿起病,肾脏病理光镜提示轻度系膜增生性肾小球肾炎,电镜提示薄基底膜肾病,听力检测提示左耳轻度感音神经性耳聋,基因检测提示COL4A5基因c.555(exon10)-c.568(exon10)delTGGTCCCACTGGTA(移码突变),导致氨基酸改变p.P185Pfs*26,家系验证其为新发突变,父母均未携带,根据美国医学遗传学与基因组学学会(ACMG)指南,该突变类型为致病性突变。HGMDpro数据库该位点未见报道。此外还检测到GJB2基因存在c.109(exon2)G>A(错义突变),导致氨基酸改变p.V37I,家系验证父母均为携带者,根据ACMG指南,该突变类型为致病性突变。HGMDpro数据库该位点已有文献报道。结论 Alport综合征及GJB2基因突变都会导致听力损伤,当Alport综合征患儿出现听力损伤时,不仅需要考虑与原发疾病相关,同时也需要警惕有无其他合并疾病,避免漏诊及误诊。

Clinical characteristics and genotype analysis of the child with Alport syndrome with GJB2 gene mutation-induced deafness: A case report and literature review

Objective To explore the clinical characteristics and genotype of children with Alport syndrome (AS) combined with gap junction protein beta 2 (GJB2) gene mutation induced-deafness. Methods A retrospective analysis of the clinical data and genetic testing results of one child with AS, who admitted to the Department of Nephrology, Xi'an Children's Hospital was performed. Results The children (female) was 3 years old and 8 months old, and the disease started with hematuria and proteinuria. Renal pathology revealed mild mesangial proliferative glomerulonephritis by light microscopy (LM), thin basement membrane nephropathy (TBMN) by electron microscopy (EM), and mild sensorineural deafness in the left ear by hearing test. Genetic testing indicated the presence of C.555 (exon10) -C.568 (exon10) delTGGTCCCACTGGTA (framesshift mutation) in collagen type Ⅳ alpha 5 chain (COL4A5) gene, leading to amino acid change p.P185Pfs*26. The mutation was verified as a new mutation in the family, and neither parent carried it. The American College of Medical Genetics and Genomics (ACMG) guidelines indicated that this mutation type was a pathogenic mutation. This locus had not been reported in the human gene mutation database (HGMDpro). In addition, c.109 (exon2) G > A (missense mutation) in GJB2 gene was also detected, leading to amino acid change p. V37I. Both parents were carriers in the family verification. According to the ACMG guidelines, this mutation type was a pathogenic mutation. This locus had been reported in HGMDpro database. Conclusion Both Alport syndrome and GJB2 gene mutation can lead to hearing loss. When hearing loss in children with AS, we should not only consider the primary disease, but also be alert to the presence of other comorbidities to avoid missed diagnosis and misdiagnosis.