دورية أكاديمية
Importance of the biochemical investigations for the functional characterization of a NPC1 variant identified by exome sequencing.
| العنوان: | Importance of the biochemical investigations for the functional characterization of a NPC1 variant identified by exome sequencing. |
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| المؤلفون: | Almenabawy N; Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada., Hung C; Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada., Sosova I; Alberta Newborn Screening and Biochemical Genetics Laboratory, University of Alberta Hospital, Alberta Precision Laboratories, Edmonton, Alberta, Canada.; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada., Mercimek-Andrews S; Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada. |
| المصدر: | American journal of medical genetics. Part A [Am J Med Genet A] 2024 Aug; Vol. 194 (8), pp. e63595. Date of Electronic Publication: 2024 Mar 29. |
| نوع المنشور: | Case Reports; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Hoboken, N.J. : Wiley-Blackwell Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| مواضيع طبية MeSH: | Niemann-Pick C1 Protein*/genetics , Niemann-Pick Disease, Type C*/genetics , Niemann-Pick Disease, Type C*/diagnosis , Niemann-Pick Disease, Type C*/pathology , Exome Sequencing* , Phenotype*, Humans ; Male ; Intracellular Signaling Peptides and Proteins/genetics ; Mutation/genetics ; Infant |
| مستخلص: | Niemann-Pick disease type C (NPC) is one of the lysosomal storage disorders. It is caused by biallelic pathogenic variants in NPC1 or NPC2, which results in a defective cholesterol trafficking inside the late endosome and lysosome. There is a high clinical variability in the age of presentation and the phenotype of this disorder making the diagnosis challenging. Here, we report a patient with an infantile onset global developmental delay, microcephaly and dysmorphic features, homozygous for c.3560C>T (p.A1187V) variant in NPC1. His plasma oxysterol levels were normal on two occasions. His lyso-sphingomyelin-509 (lyso-SM 509) and urinary bile acid levels were normal. Based on the phenotype and biochemical features, the diagnosis of NPC was excluded in this patient. We emphasize the importance of functional characterization in the classification of novel variants to prevent a misdiagnosis. Matching the phenotype and biochemical evidence with the molecular genomic tests is crucial for the confirmation of genetic diagnoses. (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.) |
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| فهرسة مساهمة: | Keywords: Niemann–Pick type C; biomarker; developmental delay; exome sequencing; oxysterol |
| المشرفين على المادة: | 0 (Niemann-Pick C1 Protein) 0 (NPC1 protein, human) 0 (Intracellular Signaling Peptides and Proteins) |
| تواريخ الأحداث: | Date Created: 20240329 Date Completed: 20240704 Latest Revision: 20240813 |
| رمز التحديث: | 20240813 |
| DOI: | 10.1002/ajmg.a.63595 |
| PMID: | 38549495 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1552-4833 |
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| DOI: | 10.1002/ajmg.a.63595 |