Division of Nephrology, Saitama Children's Medical Center.
Division of Pediatrics, Juntendo Nerima Hospital.
Tohoku J Exp Med. 2019 Sep;249(1):29-32. doi: 10.1620/tjem.249.29.
Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is characterized by primary ciliary dysfunction (ciliopathy) and progresses to end-stage kidney disease (ESKD) during the second decade of life (juvenile and adolescent NPHP) or before the age of 3 years (infantile NPHP). Here we describe the case of an infant with NPHP who carries a homozygous mutation in SDCCAG8 (also called NPHP10 or BBS16) that encodes SDCCAG8 (serologically defined colon cancer antigen 8). SDCCAG8 is localized at the centrioles of both renal epithelial cells and retinal photoreceptor cells. A mutation in SDCCAG8 is also associated with Bardet-Biedl syndrome (BBS), characterized by NPHP, obesity, polydactyly, and rod-cone dystrophy. A 2-year-old boy was referred to our hospital due to kidney dysfunction of unknown etiology; the patient presented with delayed development and opsoclonus but did not exhibit the clinical characteristics of BBS. Histological findings such as dilatation of tubules and irregular thickness of tubular basement membrane confirmed the diagnosis of NPHP. Four months after referral, the patient's renal function was rapidly deteriorated, and emergency peritoneal dialysis was initiated. Next-generation sequencing (NGS) was performed, showing that the patient carries a homozygous four-base-pair deletion in SDCCAG8 (c.849_852delTTTG, p.Cys283Ter). The patient's parents were also found to be heterozygous for this loss-of-function mutation. To the best of our knowledge, the present patient is the first case of biopsy-proven infantile NPHP with a homozygous SDCCAG8 mutation. We conclude that NGS is extremely useful in the identification of SDCCAG8-related NPHP as a cause of sudden-onset ESKD during infancy.
先天性肾病综合征（NPHP）是一种常染色体隐性遗传囊性肾病，其特征为原发性纤毛功能障碍（纤毛病），并在生命的第二个十年（青少年 NPHP）或 3 岁之前进展为终末期肾病（ESKD）（婴儿型 NPHP）。在这里，我们描述了一例携带 SDCCAG8 （也称为 NPHP10 或 BBS16）纯合突变的婴儿 NPHP 病例，该突变编码 SDCCAG8（血清定义的结肠癌抗原 8）。SDCCAG8 定位于肾上皮细胞和视网膜光感受器细胞的中心粒。SDCCAG8 的突变也与 Bardet-Biedl 综合征（BBS）相关，其特征为 NPHP、肥胖、多指（趾）畸形和视杆-视锥营养不良。一名 2 岁男孩因不明病因的肾功能障碍而被转诊至我院就诊；该患者表现为发育迟缓、眼球震颤，但未出现 BBS 的临床特征。管状扩张和管状基底膜不规则厚度等组织学发现证实了 NPHP 的诊断。转诊后 4 个月，患者的肾功能迅速恶化，开始进行紧急腹膜透析。进行下一代测序（NGS），显示患者携带 SDCCAG8 中四碱基对缺失的纯合子（c.849_852delTTTG，p.Cys283Ter）。患者的父母也被发现为该失功能突变的杂合子。据我们所知，目前的患者是首例经活检证实的婴儿型 NPHP 伴 SDCCAG8 纯合突变病例。我们的结论是，NGS 对于识别 SDCCAG8 相关 NPHP 作为婴儿期突发性 ESKD 的原因非常有用。
