Kılıç Yıldırım, G;
Yarar, C;
Şeker Yılmaz, B;
Ceylaner, S;
(2022)
Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family.
Journal of Pediatric Endocrinology and Metabolism
, 35
(4)
pp. 535-541.
10.1515/jpem-2021-0052.
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Abstract
Objectives: Niemann–Pick type C (NPC) disease is a rare progressive neurodegenerative condition that is characterized by the accumulation of cholesterol, glycosphingolipids, and sphingosine in lysosomes. Patients have various systemic and neurological findings depending on their age at onset. This disease is caused by the autosomal recessive transmission of mutations in the NPC1 and NPC2 genes; patients have mutations mainly in the NPC1 gene (95%) and the majority of them are point mutations located in the exonic regions. // Case presentation: Here, we presented three cousins with hepatosplenomegaly and progressive neurodegeneration who were diagnosed with visceral-neurodegenerative NPC disease. Their parents were relatives, and they had a history of sibling death with similar complaints. Bone marrow smear showed foamy cells in patient 1. Vertical supranuclear gaze palsy was not present in all cases. Sphingomyelinase (SM) activities were almost normal to exclude NPA or NPB. Filipin staining was performed in patient 2 and showed a massive accumulation of unesterified cholesterol The NPC1 gene analysis of the three patients showed a novel homozygous c.1553+5G>A intronic mutation. cDNA analysis was performed from the patient 3 and both parents. It was observed that exon 9 was completely skipped in the homozygous mutant baby. Both the normal and the exon 9-skipped transcripts have been detected in the parents. // Conclusions: When combined with the filipin staining and the patients’ clinical outcomes, this mutation is likely to be deleterious. Moreover, cDNA sequencing supports the pathogenicity of this novel variant.
| Type: | Article |
|---|---|
| Title: | Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1515/jpem-2021-0052 |
| Publisher version: | https://doi.org/10.1515/jpem-2021-0052 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher's terms and conditions. |
| Keywords: | filipin test; neurodegeneration; Niemann-Pick Type C (NPC); novel mutation; NPC1gene |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10140804 |
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