Ma Qian, Wu Jinlin, Che Lingyi, Kong Xiangdong
Center of Genetic and Prenatal Diagnosis, Department of Gynecology and Obstetrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 May 10;38(5):461-464. doi: 10.3760/cma.j.cn511374-20200607-00415.
To explore the genetic basis for a Chinese pedigree affected with X-linked hereditary Alport syndrome.
Next generation sequencing was carried out for the pedigree. Candidate variant was validated by Sanger sequencing. Pathological changes of renal basement membrane and expression of COL4A5 protein were analyzed by renal biopsy and immunofluorescence assay, respectively.
All patients from the pedigree manifested progressive renal damage, gross hematuria, proteinuria and nephrotic syndrome. Renal biopsy of the proband revealed thickening of the basement membrane. No expression of the COL4A5 gene was detected by immunofluorescence. High-throughput sequencing and Sanger sequencing indicated that the proband has carried a c.3706delC (p.1236Pfs*69) variant in exon 41 of the COL4A5 gene. The same variant was also found in his mother and two brothers whom were similarly affected.
The novel c.3706delC (p.1236Pfs*69) variant of the COL4A5 gene probably underlay the pathogenesis of X-linked hereditary Alport syndrome in this pedigree. Above findings have enriched the spectrum of COL4A5 gene variants and provided a basis for the diagnosis and genetic counseling for the pedigree.
探究一个患X连锁遗传性奥尔波特综合征的中国家系的遗传基础。
对该家系进行二代测序。候选变异通过桑格测序进行验证。分别通过肾活检和免疫荧光分析检测肾基底膜的病理变化及COL4A5蛋白的表达。
该家系所有患者均表现为进行性肾损害、肉眼血尿、蛋白尿和肾病综合征。先证者的肾活检显示基底膜增厚。免疫荧光未检测到COL4A5基因的表达。高通量测序和桑格测序表明先证者在COL4A5基因第41外显子携带一个c.3706delC（p.1236Pfs*69）变异。在其母亲和两名同样患病的兄弟中也发现了相同变异。
COL4A5基因新的c.3706delC（p.1236Pfs*69）变异可能是该家系X连锁遗传性奥尔波特综合征发病机制的基础。上述发现丰富了COL4A5基因变异谱，为该家系的诊断和遗传咨询提供了依据。
