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CTNS mRNA molecular analysis revealed a novel mutation in a child with infantile nephropathic cystinosis: a case report.
Papizh, Svetlana; Serzhanova, Victoria; Filatova, Alexandra; Skoblov, Mikhail; Tabakov, Vyacheslav; van den Heuvel, Lambert; Levtchenko, Elena; Prikhodina, Larisa.
Afiliación
  • Papizh S; Department of hereditary and acquired kidney diseases, Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Medical University, 125412, Taldomskaya st., 2, Moscow, Russia. papijsveta@mail.ru.
  • Serzhanova V; Research Centre for Medical Genetics, 115522, Russia, Moscow.
  • Filatova A; Research Centre for Medical Genetics, 115522, Russia, Moscow.
  • Skoblov M; Research Centre for Medical Genetics, 115522, Russia, Moscow.
  • Tabakov V; Research Centre for Medical Genetics, 115522, Russia, Moscow.
  • van den Heuvel L; Department of Pediatrics/Pediatric Nephrology, University Hospital Gasthuisberg, Leuven, Belgium.
  • Levtchenko E; Department of Pediatrics/Pediatric Nephrology, University Hospital Gasthuisberg, Leuven, Belgium.
  • Prikhodina L; Department of hereditary and acquired kidney diseases, Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Medical University, 125412, Taldomskaya st., 2, Moscow, Russia.
BMC Nephrol ; 20(1): 400, 2019 10 31.
Article en En | MEDLINE | ID: mdl-31672123
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Cistinosis / Sistemas de Transporte de Aminoácidos Neutros / Mutación Tipo de estudio: Prognostic_studies Límite: Child, preschool / Humans / Infant / Male Idioma: En Revista: BMC Nephrol Asunto de la revista: NEFROLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Rusia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Cistinosis / Sistemas de Transporte de Aminoácidos Neutros / Mutación Tipo de estudio: Prognostic_studies Límite: Child, preschool / Humans / Infant / Male Idioma: En Revista: BMC Nephrol Asunto de la revista: NEFROLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Rusia