Endreffy Emoke, Ondrik Zoltán, Kemény Eva, Vas Zoltán, Maróti Zoltán, Lencse Gerda, Bereczki Csaba, Haszon Ibolya, Túri Sándor, Iványi Béla
Szegedi Tudományegyetem, Szent-Györgyi Albert Orvos es Gyógyszerésztudományi Centrum, Altalános Orvostudományi Kar, Gyermekgyógyászati Klinika es Gyermekegészségügyi Központ, Szeged.
Orv Hetil. 2005 Dec 25;146(52):2647-53.
Collagen type IV nephropathy includes the Goodpasture syndrome, thin basement membrane nephropathy and the Alport syndrome. Mutations in the coding Col(IV)A3/A4 and Col(IV)A5 genes are probable causes of the latter two. Thin basement membrane nephropathy is mostly familial and has an autosomal dominant inheritance, at least 40% of the families have hematuria that co-segregates with the Col(IV)A3 and/or Col(IV)A4 loci. 85% of Alport syndrome cases are transmitted as an X-linked semidominant form due to Col(IV)A5 mutations. About 14% of Alport syndrome cases exhibit autosomal recessive, and 1% autosomal dominant inheritance, both caused by mutations in the Col(IV)A3 or Col(IV)A4 genes in boys and in girls.
The co-segregation pattern of hematuria was examined in two families with thin basement membrane nephropathy and one family with the Alport syndrome, using short tandem repeat markers, spanning the Col(IV)A3/A4 and Col(IV)A5 loci to assess their linkage to the clinical symptoms and morphological alterations in the renal biopsy specimens.
Markers: Col(IV)A3: CAll and D2S401; Col(IV)A4: HaeIII/RFLP; and Col(IV)A5: DXS456, 2B6 and 2B20.
The hematuria displayed autosomal dominant inheritance and co-segregated with Col(IV)A3 markers in one of the thin basement membrane nephropathy families. In the second, the hematuria did not segregate with the Col(IV)A3/A4 or Col(IV)A5 loci, suggesting the possibility of another genetic locus for the disease. The Alport syndrome exhibited autosomal recessive inheritance and did not link to Col(IV)A5 markers, and the Col(IV)A3/A4 markers were informative only in part.
Knowledge of the inheritance and genetic background of collagen type IV nephropathy will be very important in the diagnostics and genetic counseling in the future.
IV型胶原肾病包括Goodpasture综合征、薄基底膜肾病和Alport综合征。编码Col(IV)A3/A4和Col(IV)A5基因的突变可能是后两种疾病的病因。薄基底膜肾病大多为家族性，呈常染色体显性遗传，至少40%的家族中血尿与Col(IV)A3和/或Col(IV)A4基因座共分离。85%的Alport综合征病例因Col(IV)A5突变呈X连锁半显性遗传。约14%的Alport综合征病例表现为常染色体隐性遗传，1%为常染色体显性遗传，均由男孩和女孩的Col(IV)A3或Col(IV)A4基因突变引起。
利用短串联重复序列标记物检测两个薄基底膜肾病家族和一个Alport综合征家族中血尿的共分离模式，这些标记物跨越Col(IV)A3/A4和Col(IV)A5基因座，以评估它们与肾活检标本中临床症状和形态学改变的连锁关系。
标记物：Col(IV)A3：CAll和D2S401；Col(IV)A4：HaeIII/RFLP；Col(IV)A5：DXS456、2B6和2B20。
在一个薄基底膜肾病家族中，血尿呈常染色体显性遗传，并与Col(IV)A3标记物共分离。在另一个家族中，血尿与Col(IV)A3/A4或Col(IV)A5基因座不分离，提示该疾病可能存在另一个基因座。Alport综合征表现为常染色体隐性遗传，与Col(IV)A5标记物无连锁关系，Col(IV)A3/A4标记物仅部分具有信息价值。
了解IV型胶原肾病的遗传方式和遗传背景对未来的诊断和遗传咨询非常重要。
