Whole exome sequencing identification of a novel insertion mutation in the phospholipase C ε‑1 gene in a family with steroid resistant inherited nephrotic syndrome

Hashmi,Jamil  Amjad; Safar,Ramziah  Ahmed; Afzal,Sibtain; Albalawi,Alia  M.; Abdu‑Samad,Feroz; Iqbal,Zafar; Basit,Sulman

doi:10.3892/mmr.2018.9528

Whole exome sequencing identification of a novel insertion mutation in the phospholipase C ε‑1 gene in a family with steroid resistant inherited nephrotic syndrome

Authors:
- Jamil Amjad Hashmi
- Ramziah Ahmed Safar
- Sibtain Afzal
- Alia M. Albalawi
- Feroz Abdu‑Samad
- Zafar Iqbal
- Sulman Basit
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Affiliations: Center for Genetics and Inherited Diseases, Taibah University, Medina 42318, Kingdom of Saudi Arabia, Department of Nephrology, Madinah Maternity and Children Hospital, Medina 42319, Kingdom of Saudi Arabia, Prince Naif Centre for Immunology Research, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh 12372, Kingdom of Saudi Arabia, College of Applied Medical Sciences, National Guard Health Affairs, Al‑Ahsa 36428, Kingdom of Saudi Arabia
Published online on: October 2, 2018 https://doi.org/10.3892/mmr.2018.9528
Pages: 5095-5100

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Abstract

Nephrotic syndrome (NS) represents a heterogeneous group of kidney disorders characterized by excessive proteinuria, hypoalbuminemia and edema. Defects in the filtration barrier of the glomeruli results in the development of NS. The genetic cause of NS remains to be fully elucidated. However, previous studies based on positional cloning of genes mutated in NS have provided limited insight into the pathogenesis of this disease. Mutations in phospholipase C ε‑1 (PLCE1) have been reported as a cause of early onset NS characterized by histology of diffuse mesangial sclerosis. In the present study, the underlying cause of NS in a consanguineous family was identified. Clinical and molecular aspects of a consanguineous Saudi family comprised of five individuals with steroid resistant NS were examined. Seven healthy individuals from the same family were also studied. Whole exome sequencing (WES) was performed to detect the genetic defect underlying NS. WES identified a homozygous novel insertion mutation (c.6272_6273insT) in the PLCE1 gene. Pedigree and segregation analysis confirmed an autosomal recessive inheritance pattern. This mutation may result in a bi‑allelic loss of the C‑terminal Ras‑associating domain in PLCE1 that results in NS. The present study expanded the mutational spectrum of PLCE1 in NS. In addition, the present study provided further evidence that supports the important involvement of PLCE1 in the physiological function of the glomerular filtration barrier.

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