Novel Sequence Variants in the NPC1 Gene in Egyptian Patients with Niemann-Pick Type C

Mona L. Essawi; Asmaa F. Abdel-aleem; Mohamed A. Badawy; Maha S. Zaki; Magda F. Mohamed; Heba A. Hassan; Ekram M. Fateen

doi:10.3889/oamjms.2020.4626

Authors

Mona L. Essawi Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
Asmaa F. Abdel-aleem Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
Mohamed A. Badawy Department of Organic Chemistry, Faculty of Science, Cairo University, Giza, Egypt
Maha S. Zaki Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
Magda F. Mohamed Department of Chemistry (Biochemistry Branch), Faculty of Science, Cairo University, Giza, Egypt; Department of Chemistry,Faculty of Science and Arts, Khulais, University of Jeddah,Jeddah, Saudi Arabia
Heba A. Hassan Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
Ekram M. Fateen Department of Biochemical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt

DOI:

https://doi.org/10.3889/oamjms.2020.4626

Keywords:

Niemann-Pick disease type C, NPC1 gene, NPC2 gene, Hot spot residues

Abstract

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, progressive neuro-visceraldisease caused by biallelic mutations in either NPC1gene (95% of cases) or NPC2 gene.

AIM: This caseseries study aimed at the molecular analysis of certain hot spots of NPC1 genein NPC Egyptian patients.

METHODS: The study included 15 unrelated NPC patients and selected parents,as well as20 healthy controls of matched sex and age. Clinical investigations were performed according to well established clinical criteria. Assessment of the chitotriosidase level, as an initial screening tool for NPC, was done in all cases. Polymerase chain reaction amplification of NPC1 exons (17–25) encountering the hotspot residues (855–1098 and1038–1253) was carried out followed by direct sequencingfor mutational analysis.

RESULTS: All includedpatients with mainly neurovisceral involvement were characterized. The onset of the disease varied from early-infantile (58.3%) to late-infantile (26.7%) and juvenile-onset (6.7%). Ahigh chitotriosidase level wasobservedin all patients. Molecular analysis of NPC1 (exons 17–25) confirmed 15 mutant alleles out of 30 studied ones. They included two novel homozygous missense variants (p.Ser1169Arg and p.Ser1197Phe) and previously reportedfour mutations (p.Arg958*, p.Gly910Ser, p.Ala927Glyfs*38, and andp.Cys1011*).

CONCLUSION: The two studied amino acid residues (855–1098 and 1038–1253) could beconsidered aspotential hotspot regions in NPC1 Egyptian patients.

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