Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus N, Denmark.
Department of Clinical Medicine, Child and Youth Research Laboratory, Aarhus University, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus N, Denmark.
Eur J Pediatr. 2020 Sep;179(9):1481-1486. doi: 10.1007/s00431-020-03634-3. Epub 2020 Mar 20.
Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood. Cases with the familial occurrence of SSNS suggest that genetics may play a role in the disease. Human leucocyte antigen (HLA) alleles have been associated with SSNS. We present genetic findings in nine families (44 participants), each with at least two affected siblings. A total of 19 patients were affected with familial SSNS. Six of nine families showed linkage to markers on chromosome 6p (27.29-33.97 Mbp) (Hg19), especially to markers D6S1629 and D6S1560 on HLA dense region in this location. Interestingly, we also found linkage of disease phenotype of familial SSNS on chromosome 15 (91.7-96.9 Mbp) (Hg19) with a logarithm of odds (LOD) score Z = 3.02.Conclusion: Our findings confirm the linkage of HLA markers on chromosome 6, which strengthens the association of HLA alleles in SSNS. What is Known: • Human leukocyte antigen (HLA) alleles have been associated with idiopathic steroid-sensitive nephrotic syndrome (SSNS). Only few studies have investigated the association between HLA alleles and familial SSNS. What is New: • We present evidence of linkage of familial SSNS to chromosome 6p (27.29-33.97 Mbp) (Hg19), especially to markers D6S1629 and D6S1560 on HLA dense region in this location. We also found linkage of the disease phenotype of familial SSNS on chromosome 15 (91.7-96.9 Mbp) (Hg19) with a logarithm of odds (LOD) score of Z = 3.02 following autosomal recessive inheritance pattern.
激素敏感型肾病综合征 (SSNS) 是儿童中最常见的肾病综合征形式。家族性 SSNS 病例表明，遗传可能在疾病中起作用。人类白细胞抗原 (HLA) 等位基因与 SSNS 有关。我们报告了 9 个家族（44 名参与者）的遗传发现，每个家族至少有 2 名受影响的兄弟姐妹。共有 19 名患者患有家族性 SSNS。9 个家族中的 6 个家族显示与染色体 6p（27.29-33.97 Mbp）（Hg19）上的标记物（特别是位于该位置 HLA 密集区的标记物 D6S1629 和 D6S1560）有连锁。有趣的是，我们还发现染色体 15（91.7-96.9 Mbp）（Hg19）上的家族性 SSNS 疾病表型与疾病表型也有连锁（对数优势 (LOD) 评分 Z = 3.02）。结论：我们的研究结果证实了 HLA 标记物在染色体 6 上的连锁，这加强了 HLA 等位基因在 SSNS 中的关联。已知：•人类白细胞抗原 (HLA) 等位基因与特发性激素敏感型肾病综合征 (SSNS) 有关。只有少数研究调查了 HLA 等位基因与家族性 SSNS 之间的关系。新发现：•我们提供了家族性 SSNS 与染色体 6p（27.29-33.97 Mbp）（Hg19）连锁的证据，特别是位于该位置 HLA 密集区的标记物 D6S1629 和 D6S1560。我们还发现，根据常染色体隐性遗传模式，染色体 15（91.7-96.9 Mbp）（Hg19）上的家族性 SSNS 疾病表型与对数优势 (LOD) 评分 Z = 3.02 之间存在连锁。
