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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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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