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

Authors:
Jiro Kino
Jiro Kino
Kansai Medical University
Japan
Hiroyasu Tsukaguchi
Hiroyasu Tsukaguchi
University of Tokushima
Takahisa Kimata
Takahisa Kimata
Kansai Medical University
Huan Thanh Nguyen
Huan Thanh Nguyen
Kansai Medical University
Hirakata | Japan
Yorika Nakano
Yorika Nakano
Kansai Medical University
Japan
Noriko Miyake
Noriko Miyake
Yokohama City University Graduate School of Medicine
Yokohama | Japan
Naomichi Matsumoto
Naomichi Matsumoto
Yokohama City University Graduate School of Medicine
Yokohama | Japan
Kazunari Kaneko
Kazunari Kaneko
Kansai Medical University
Japan

BMC Nephrol 2017 Jul 6;18(1):220. Epub 2017 Jul 6.

Department of Pediatrics, Kansai Medical University, 2-5-1 Shimachi, Hirakata, Osaka, 573-1010, Japan.

Background: Congenital 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 Presentations: An 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.

Conclusions: Our 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.
PDF Download - Full Text Link
( Please be advised that this article is hosted on an external website not affiliated with PubFacts.com)
Source Status
http://dx.doi.org/10.1186/s12882-017-0632-4DOI ListingPossible
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501564PMCFound
July 2017
6 Reads

Similar Publications

Simultaneous mutations of LAMB2 and NPHP1genes in a Chinese girl with isolated congenital nephrotic syndrome: a case report.

BMC Pediatr 2016 Mar 22;16:44. Epub 2016 Mar 22.

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, China.

Background: LAMB2 mutations cause Pierson syndrome (OMIM 609049), an autosomal recessive genetic disease typically characterized by congenital nephrotic syndrome (CNS) and early onset renal failure, as well as bilateral microcoria. NPHP1 mutations cause familial juvenile nephronophthisis type 1 (NPHP1, OMIM 256100), another autosomal recessive renal disease that usually occurs years after birth. Both Pierson syndrome and nephronophthisis cause end-stage renal disease and rare kidney diseases in children. Read More

View Article
March 2016

A novel LAMB2 gene mutation associated with a severe phenotype in a neonate with Pierson syndrome.

Eur J Med Res 2016 Apr 30;21:19. Epub 2016 Apr 30.

Division of Pediatric Nephrology, Department of Pediatrics, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.

Background: Pierson syndrome (PS) is a rare autosomal recessive disorder, caused by mutations in the laminin β2 (LAMB2) gene. It is characterized by congenital nephrotic syndrome, microcoria, and neurodevelopmental deficits. Several mutations with genotype-phenotype correlations have been reported, often with great clinical variability. Read More

View Article
April 2016

LAMB2 mutation with different phenotypes in China
.

Clin Nephrol 2017 Jan;87 (2017)(1):33-38

Background: Mutations of the LAMB2 gene mainly cause Pierson syndrome (OMIM) #609049), characterized by congenital nephrotic syndrome (CNS) and complex ocular involvements with microcoria as the most prominent clinical feature. However, the phenotypic spectrum of LAMB2-associated disorders is broader, isolated congenital or infantile nephrotic syndrome can also be seen. The aim of this study was to explore the phenotypes of different LAMB2 mutations in China. Read More

View Article
January 2017

A novel mutation of laminin β-2 gene in Pierson syndrome manifested with nephrotic syndrome in the early neonatal period.

Genet Couns 2013 ;24(2):141-7

Departmentof Neonatology, Dr Sami Ulus Maternity and Children Training and Research Hospital, Ankara, Turkey.

Pierson syndrome is a rare autosomal recessive disorder which is mainly characterized by congenital nephrotic syndrome (CNS), diffuse mesangial sclerosis (DMS) and distinct ocular abnormalities, including microcoria. Most affected children exhibit early onset of chronic renal failure, neurodevelopmental deficits, and blindness. It is caused by a homozygous or compound heterozygous mutation in the gene encoding laminin beta2 (LAMB2) on chromosome 3p21. Read More

View Article
October 2013