CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report

Abstract Background Cystinosis is an autosomal recessive lysosomal storage disorder characterized by accumulation of cystine in lysosomes throughout the body. Cystinosis is caused by mutations in the CTNS gene that encodes the lysosomal cystine carrier protein cystinosin. CTNS mutations result in ei...

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Main Authors: Svetlana Papizh, Victoria Serzhanova, Alexandra Filatova, Mikhail Skoblov, Vyacheslav Tabakov, Lambert van den Heuvel, Elena Levtchenko, Larisa Prikhodina
Format: Article
Language:English
Published: BMC 2019-10-01
Series:BMC Nephrology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12882-019-1589-2
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spelling doaj-5f9219c6abe147369c8d32e14aeaa2dc2020-11-25T04:01:46ZengBMCBMC Nephrology1471-23692019-10-012011610.1186/s12882-019-1589-2CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case reportSvetlana Papizh0Victoria Serzhanova1Alexandra Filatova2Mikhail Skoblov3Vyacheslav Tabakov4Lambert van den Heuvel5Elena Levtchenko6Larisa Prikhodina7Department of hereditary and acquired kidney diseases, Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Medical UniversityResearch Centre for Medical GeneticsResearch Centre for Medical GeneticsResearch Centre for Medical GeneticsResearch Centre for Medical GeneticsDepartment of Pediatrics/Pediatric Nephrology, University Hospital GasthuisbergDepartment of Pediatrics/Pediatric Nephrology, University Hospital GasthuisbergDepartment of hereditary and acquired kidney diseases, Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Medical UniversityAbstract Background Cystinosis is an autosomal recessive lysosomal storage disorder characterized by accumulation of cystine in lysosomes throughout the body. Cystinosis is caused by mutations in the CTNS gene that encodes the lysosomal cystine carrier protein cystinosin. CTNS mutations result in either complete absence or reduced cystine transporting function of the protein. The diagnosis of nephropathic cystinosis is generally based on measuring leukocyte cystine level, demonstration of corneal cystine crystals by the slit lamp examination and confirmed by genetic analysis of the CTNS gene. Case presentation A boy born to consanguineous Caucasian parents had the characteristic clinical features of the infantile nephropathic cystinosis including renal Fanconi syndrome (polydipsia/polyuria, metabolic acidosis, hypokalemia, hypophosphatemia, low molecular weight proteinuria, glycosuria, cystine crystals in the cornea) and elevated WBC cystine levels. Initially we performed RFLP analysis of the common in the Northern European population 57-kb deletion of proband’s DNA, then a direct Sanger sequencing which revealed no mutations in the coding part of the CTNS gene. To confirm the diagnosis we performed RT-PCR analysis of total RNA obtained from patient-derived fibroblasts in combination with cDNA sequencing. This revealed the skipping of exon 4 and exon 5 in the CTNS in our patient. Therefore, we detected a novel 9-kb homozygous deletion in the CTNS gene at genomic DNA level, spanning region from intron 3 to intron 5. In order to identify the inheritance pattern of the deletion we analyzed DNA of proband’s mother and father. Both parents were found to be heterozygous carriers of the CTNS mutation. Conclusions Analysis of CTNS gene transcript allowed to identify a large homozygous deletion in the patient with infantile nephropathic cystinosis. Mutational detection at RNA level may be an efficient tool to establish the genetic defect in some cystinosis patients.http://link.springer.com/article/10.1186/s12882-019-1589-2Nephropathic cystinosisFanconi syndromeCTNSmRNA analysis
collection DOAJ
language English
format Article
sources DOAJ
author Svetlana Papizh
Victoria Serzhanova
Alexandra Filatova
Mikhail Skoblov
Vyacheslav Tabakov
Lambert van den Heuvel
Elena Levtchenko
Larisa Prikhodina
spellingShingle Svetlana Papizh
Victoria Serzhanova
Alexandra Filatova
Mikhail Skoblov
Vyacheslav Tabakov
Lambert van den Heuvel
Elena Levtchenko
Larisa Prikhodina
CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report
BMC Nephrology
Nephropathic cystinosis
Fanconi syndrome
CTNS
mRNA analysis
author_facet Svetlana Papizh
Victoria Serzhanova
Alexandra Filatova
Mikhail Skoblov
Vyacheslav Tabakov
Lambert van den Heuvel
Elena Levtchenko
Larisa Prikhodina
author_sort Svetlana Papizh
title CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report
title_short CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report
title_full CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report
title_fullStr CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report
title_full_unstemmed CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report
title_sort ctns mrna molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report
publisher BMC
series BMC Nephrology
issn 1471-2369
publishDate 2019-10-01
description Abstract Background Cystinosis is an autosomal recessive lysosomal storage disorder characterized by accumulation of cystine in lysosomes throughout the body. Cystinosis is caused by mutations in the CTNS gene that encodes the lysosomal cystine carrier protein cystinosin. CTNS mutations result in either complete absence or reduced cystine transporting function of the protein. The diagnosis of nephropathic cystinosis is generally based on measuring leukocyte cystine level, demonstration of corneal cystine crystals by the slit lamp examination and confirmed by genetic analysis of the CTNS gene. Case presentation A boy born to consanguineous Caucasian parents had the characteristic clinical features of the infantile nephropathic cystinosis including renal Fanconi syndrome (polydipsia/polyuria, metabolic acidosis, hypokalemia, hypophosphatemia, low molecular weight proteinuria, glycosuria, cystine crystals in the cornea) and elevated WBC cystine levels. Initially we performed RFLP analysis of the common in the Northern European population 57-kb deletion of proband’s DNA, then a direct Sanger sequencing which revealed no mutations in the coding part of the CTNS gene. To confirm the diagnosis we performed RT-PCR analysis of total RNA obtained from patient-derived fibroblasts in combination with cDNA sequencing. This revealed the skipping of exon 4 and exon 5 in the CTNS in our patient. Therefore, we detected a novel 9-kb homozygous deletion in the CTNS gene at genomic DNA level, spanning region from intron 3 to intron 5. In order to identify the inheritance pattern of the deletion we analyzed DNA of proband’s mother and father. Both parents were found to be heterozygous carriers of the CTNS mutation. Conclusions Analysis of CTNS gene transcript allowed to identify a large homozygous deletion in the patient with infantile nephropathic cystinosis. Mutational detection at RNA level may be an efficient tool to establish the genetic defect in some cystinosis patients.
topic Nephropathic cystinosis
Fanconi syndrome
CTNS
mRNA analysis
url http://link.springer.com/article/10.1186/s12882-019-1589-2
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