Nephron development and extrarenal features in a child with congenital nephrotic syndrome caused by null LAMB2 mutations

BMC Nephrology

Case Report

Noriko Miyake¹  Naomichi Matsumoto¹  Yorika Nakano²  Kazunari Kaneko³  Takahisa Kimata³  Jiro Kino³  Hiroyasu Tsukaguchi⁴  Huan Thanh Nguyen⁴ 

[1] Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3–9 Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan;Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan;Present Address: Department of Histopathology and Cytology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan;Department of Pediatrics, Kansai Medical University, 2-5-1 Shimachi, Hirakata, 573-1010, Osaka, Japan;Second Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi Hirakata, 573-1010, Osaka, Japan;

关键词: Nephrotic syndrome;    Nephron development;    Laminin;    Basement membrane;    Extracellular matrix;   

DOI  :  10.1186/s12882-017-0632-4

 received in 2016-07-31, accepted in 2017-06-22,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCongenital nephrotic syndrome (CNS) is a rare disorder caused by various structural and developmental defects of glomeruli. It occurs typically as an isolated kidney disorder but associates sometimes with other systemic, extrarenal manifestations.Case PresentationsAn infant presented with severe CNS, which progressed rapidly to renal failure at age of 3 months and death at 27 months. The clinical phenotypes and genetic causes were studied, including the renal pathology at autopsy.Besides the CNS, the affected child had remarkable right-side predominant eye-ball hypoplasia with bilateral anterior chamber dysgenesis (microcoria). Brain MRI revealed grossly normal development in the cerebrum, cerebellum, and brain stem. Auditory brainstem responses were bilaterally blunted, suggesting a defective auditory system. At autopsy, both kidneys were mildly atrophied with persistent fetal lobulation. Microscopic examination showed a diffuse global sclerosis. However, despite of the smaller size of glomeruli, the nephron number remained similar to that of the age-matched control. Whole-exome sequencing revealed that the affected child was compound heterozygous for novel truncating LAMB2 mutations: a 4-bp insertion (p.Gly1693Alafs*8) and a splicing donor-site substitution (c.1225 + 1G > A), presumably deleting the coiled-coil domains that form the laminin 5–2-1 heterotrimer complex.ConclusionsOur case represents a variation of Pierson syndrome that accompanies CNS with unilateral ocular hypoplasia. The average number but smaller glomeruli could reflect either mal-development or glomerulosclerosis. Heterogeneous clinical expression of LAMB2 defects may associate with the difference in fetal β1 subtype compensation among affected tissues. Further study is necessary to evaluate incidence and features of auditory defect under LAMB2 deficiency.

【 授权许可】

CC BY   
© The Author(s). 2017