Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family

Gonca Kılıç Yıldırım; Coşkun Yarar; Berna Şeker Yılmaz; Serdar Ceylaner

doi:10.1515/jpem-2021-0052

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Article

Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family

Gonca Kılıç Yıldırım , Coşkun Yarar , Berna Şeker Yılmaz and Serdar Ceylaner

Published/Copyright: December 10, 2021

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 4

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.

Keywords: filipin test; neurodegeneration; Niemann-Pick Type C (NPC); novel mutation; NPC1gene

Corresponding author: Gonca Kılıç Yıldırım, Assistant Professor, MD, Division of Child Nutrition and Metabolism, Department of Paediatrics, Faculty of Medicine, Eskisehir Osmangazi University, Meselik campuse, Odunpazari, Eskisehir, Turkey, Phone: +90 222 2392979 2763, +90 532 7485817, Fax: +90 222 22900644, E-mail: goncaklch@yahoo.com.

Acknowledgments

We would like to thank Professor Sultan D. Aydoğdu and we remember her with respect. The filipin test was studied at Laboratoire de Biologie Medicale Multi Sites du Chu de Lyon. Also, thanks to Marie T Vanier for her support on this issue.

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2021-01-27

Accepted: 2021-11-19

Published Online: 2021-12-10

Published in Print: 2022-04-26

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Articles in the same Issue

https://doi.org/10.1515/jpem-2021-0052

Keywords for this article

filipin test; neurodegeneration; Niemann-Pick Type C (NPC); novel mutation; NPC1gene