Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease
Niemann Pick disease type C (NPC) is a neurovisceral disorder due to mutations in <i>NPC1</i> or <i>NPC2</i>. This review focuses on poorly characterized clinical and molecular features of early infantile form of NPC (EIF) and identified 89 cases caused by <i>NPC1</i...
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/14/5059 |
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| author | Berna Seker Yilmaz Julien Baruteau Ahad A. Rahim Paul Gissen |
| author_facet | Berna Seker Yilmaz Julien Baruteau Ahad A. Rahim Paul Gissen |
| author_sort | Berna Seker Yilmaz |
| collection | DOAJ |
| description | Niemann Pick disease type C (NPC) is a neurovisceral disorder due to mutations in <i>NPC1</i> or <i>NPC2</i>. This review focuses on poorly characterized clinical and molecular features of early infantile form of NPC (EIF) and identified 89 cases caused by <i>NPC1</i> (NPC1) and 16 by <i>NPC2</i> (NPC2) mutations. Extra-neuronal features were common; visceromegaly reported in 80/89 NPC1 and in 15/16 NPC2, prolonged jaundice in 30/89 NPC1 and 7/16 NPC2. Early lung involvement was present in 12/16 NPC2 cases. Median age of neurological onset was 12 (0–24) and 7.5 (0–24) months in NPC1 and NPC2 groups, respectively. Developmental delay and hypotonia were the commonest first detected neurological symptoms reported in 39/89 and 18/89 NPC1, and in 8/16 and 10/16 NPC2, respectively. Additional neurological symptoms included vertical supranuclear gaze palsy, dysarthria, cataplexy, dysphagia, seizures, dystonia, and spasticity. The following mutations in homozygous state conferred EIF: deletion of exon 1+promoter, c.3578_3591 + 9del, c.385delT, p.C63fsX75, IVS21-2delATGC, c. 2740T>A (p.C914S), c.3584G>T (p.G1195V), c.3478-6T>A, c.960_961dup (p.A321Gfs*16) in <i>NPC1</i> and c.434T>A (p.V145E), c.199T>C (p.S67P), c.133C>T (p.Q45X), c.141C>A (p.C47X) in <i>NPC2</i>. This comprehensive analysis of the EIF type of NPC will benefit clinical patient management, genetic counselling, and assist design of novel therapy trials. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:24:16Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fa9d92dfb5a548c3b07fc8f88c46dd5c2023-11-20T07:09:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114505910.3390/ijms21145059Clinical and Molecular Features of Early Infantile Niemann Pick Type C DiseaseBerna Seker Yilmaz0Julien Baruteau1Ahad A. Rahim2Paul Gissen3Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKUCL School of Pharmacy, University College London, London WC1N 1AX, UKGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKNiemann Pick disease type C (NPC) is a neurovisceral disorder due to mutations in <i>NPC1</i> or <i>NPC2</i>. This review focuses on poorly characterized clinical and molecular features of early infantile form of NPC (EIF) and identified 89 cases caused by <i>NPC1</i> (NPC1) and 16 by <i>NPC2</i> (NPC2) mutations. Extra-neuronal features were common; visceromegaly reported in 80/89 NPC1 and in 15/16 NPC2, prolonged jaundice in 30/89 NPC1 and 7/16 NPC2. Early lung involvement was present in 12/16 NPC2 cases. Median age of neurological onset was 12 (0–24) and 7.5 (0–24) months in NPC1 and NPC2 groups, respectively. Developmental delay and hypotonia were the commonest first detected neurological symptoms reported in 39/89 and 18/89 NPC1, and in 8/16 and 10/16 NPC2, respectively. Additional neurological symptoms included vertical supranuclear gaze palsy, dysarthria, cataplexy, dysphagia, seizures, dystonia, and spasticity. The following mutations in homozygous state conferred EIF: deletion of exon 1+promoter, c.3578_3591 + 9del, c.385delT, p.C63fsX75, IVS21-2delATGC, c. 2740T>A (p.C914S), c.3584G>T (p.G1195V), c.3478-6T>A, c.960_961dup (p.A321Gfs*16) in <i>NPC1</i> and c.434T>A (p.V145E), c.199T>C (p.S67P), c.133C>T (p.Q45X), c.141C>A (p.C47X) in <i>NPC2</i>. This comprehensive analysis of the EIF type of NPC will benefit clinical patient management, genetic counselling, and assist design of novel therapy trials.https://www.mdpi.com/1422-0067/21/14/5059Niemann Pick disease type Cearly infantile onsetneurological manifestations |
| spellingShingle | Berna Seker Yilmaz Julien Baruteau Ahad A. Rahim Paul Gissen Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease International Journal of Molecular Sciences Niemann Pick disease type C early infantile onset neurological manifestations |
| title | Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease |
| title_full | Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease |
| title_fullStr | Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease |
| title_full_unstemmed | Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease |
| title_short | Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease |
| title_sort | clinical and molecular features of early infantile niemann pick type c disease |
| topic | Niemann Pick disease type C early infantile onset neurological manifestations |
| url | https://www.mdpi.com/1422-0067/21/14/5059 |
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