Human urine-derived renal epithelial cells provide insights into kidney-specific alternate splicing variants

European Journal of Human Genetics : EJHG
Elisa MolinariJohn A Sayer

Abstract

The majority of multi-exon genes undergo alternative splicing to produce different mRNA transcripts and this may occur in a tissue-specific manner. Assessment of mRNA transcripts isolated from blood samples may sometimes be unhelpful in determining the affect on function of putative splice-site variants affecting kidney-specific mRNA transcripts. Here we present data demonstrating the power of using human urine-derived renal epithelial cells (hUREC) as a source of kidney RNA. We report clinical and molecular genetic data from three affected cases from two families all with end-stage renal disease by 15 years of age. In both families, heterozygous variants which are predicted to effect function in NPHP3 were found on one allele, in combination with a synonymous SNV (c.2154C>T; p.Phe718=), 18 base pairs from the exon-intron boundary within exon 15 of NPHP3. The only mRNA transcript amplified from wild-type whole blood showed complete splicing out of exon 15. Urine samples obtained from control subjects and the father of family 2, who carried the synonymous SNV variant, were therefore used to culture hUREC and allowed us to obtain kidney-specific mRNA. Control kidney mRNA showed retention of exon 15, while the mRNA from the patien...Continue Reading

References

Jan 17, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Todd E MillerNanette H Bishopric
Jan 30, 2009·Kidney International·Kálmán ToryRémi Salomon
Nov 22, 2013·Kidney International·Heon Yung GeeFriedhelm Hildebrandt
Feb 8, 2014·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Henry FehrenbachCarsten Bergmann
May 9, 2015·Science·Marta MeléRoderic Guigó
Oct 13, 2017·Nature·UNKNOWN GTEx ConsortiumStephen B Montgomery

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Citations

Mar 7, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Elisa Molinari, John A Sayer
Apr 9, 2019·Ophthalmic Genetics·Andrew C BrowningJohn A Sayer
Jan 12, 2021·Molecular and Cellular Probes·Rebecca Marie DewhurstJohn A Sayer
Aug 17, 2019·Current Opinion in Genetics & Development·Laura A Devlin, John A Sayer
Jul 3, 2021·Cells·Tjessa BondueMohamed A Elmonem

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Methods Mentioned

BETA
biopsy

Software Mentioned

Human Splicing Finder
ClinVar
MutationTaster Human Splicing Finder

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Alternative splicing

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