Mutations in phospholipase C epsilon 1 are not sufficient to cause diffuse mesangial sclerosis
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Published on: November 22, 2024
Rodney D Gilbert1, Claire L S Turner, Jane Gibson
1Wessex Regional Paediatric Nephro-Urology Service, Southampton General Hospital, Southampton, UK. rodney.gilbert@suht.swest.nhs.uk
Insights
Mutations in phospholipase C epsilon 1 (PLCE1) cause diffuse mesangial sclerosis. However, a PLCE1 mutation may not always cause disease, suggesting other genetic factors are involved.
Area of Science:
- Genetics
- Nephrology
- Molecular Biology
Background:
- Diffuse mesangial sclerosis (DMS) is a kidney disorder that can be isolated or part of a syndrome.
- Mutations in the phospholipase C epsilon 1 (PLCE1) gene have been linked to a nonsyndromic, autosomal recessive form of DMS.
Observation:
- This study investigated three children from a Pakistani family with DMS and congenital/infantile nephrotic syndrome.
- Genome-wide single-nucleotide polymorphism mapping identified homozygous mutations in PLCE1 in all affected children.
- A four-basepair deletion in exon 3 of PLCE1, causing a premature stop codon, was found in affected individuals.
Findings:
- All affected children were homozygous for the identified PLCE1 mutation.
- An asymptomatic father was also homozygous for the same PLCE1 mutation, indicating nonpenetrance.
- This suggests that mutation within PLCE1 is not always sufficient to cause diffuse mesangial sclerosis.
Implications:
- The nonpenetrance observed may be due to compensatory mutations at a second genetic locus.
- Further research is needed to understand the genetic mechanisms underlying DMS and variable penetrance.
- Identifying genetic factors for DMS can aid in diagnosis and genetic counseling for affected families.
Abstract:
Diffuse mesangial sclerosis occurs as an isolated abnormality or as a part of a syndrome. Recently, mutations in phospholipase C epsilon 1 (PLCE1) were found to cause a nonsyndromic, autosomal recessive form of this disease. Here we describe three children from one consanguineous kindred of Pakistani origin with diffuse mesangial sclerosis who presented with congenital or infantile nephrotic syndrome. Homozygous mutations in PLCE1 (also known as KIAA1516, PLCE, or NPHS3) were identified following genome-wide mapping of single-nucleotide polymorphisms. All affected children were homozygous for a four-basepair deletion in exon 3, which created a premature translational stop codon. Analysis of the asymptomatic father of two of the children revealed that he was also homozygous for the same mutation. We conclude this nonpenetrance may be due to compensatory mutations at a second locus and that mutation within PLCE1 is not always sufficient to cause diffuse mesangial sclerosis.
