Academic Journal
New insights into the landscape of ALPL gene variants in patients with hypophosphatasia from the Global HPP Registry
| العنوان: | New insights into the landscape of ALPL gene variants in patients with hypophosphatasia from the Global HPP Registry |
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| المؤلفون: | Kishnani, Priya S., Seefried, Lothar, Dahir, Kathryn M., Martos‐Moreno, Gabriel Ángel, Linglart, Agnès, Petryk, Anna, Mowrey, William R., Fang, Shona, Ozono, Keiichi, Högler, Wolfgang, Rockman‐Greenberg, Cheryl |
| المساهمون: | Alexion Pharmaceuticals |
| المصدر: | American Journal of Medical Genetics Part A ; volume 194, issue 11 ; ISSN 1552-4825 1552-4833 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2024 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Hypophosphatasia (HPP) is a rare, inherited metabolic disease characterized by low tissue‐nonspecific alkaline phosphatase activity due to ALPL gene variants. We describe ALPL variants from the observational, prospective, multinational Global HPP Registry. Inclusion in the analysis required a diagnosis of HPP, low serum ALP activity, and ≥1 ALPL variant. Of 1176 patients enrolled as of September 2022, 814 met inclusion criteria in Europe (48.9%), North America (36.7%), Japan (10.2%), Australia (2.6%), and elsewhere (1.6%). Most patients (74.7%) had 1 ALPL variant; 25.3% had ≥2 variants. Nearly all patients (95.6%) had known disease‐causing variants; 4.4% had variants of uncertain significance. Disease‐causing variants were predominantly missense (770/1556 alleles). The most common variants were c.571G>A (102/1628 alleles), c.1250A>G (66/1628 alleles), and c.1559del (61/1628 alleles). Variant profiles were generally consistent, except in Japan, where a higher proportion of patients (68.7%) had ≥2 ALPL variants, likely because more had disease onset before age 6 months (53.0% vs. 10.1%–23.1% elsewhere). Frameshift mutations (61/164 alleles) and inframe deletions (7/164 alleles) were more common in Japan. Twenty‐three novel variants were discovered, each in a single geographic region, predominantly Europe. Analyses confirmed previously known ALPL variants, identified novel variants, and characterized geographic variation in frequency and type of ALPL variants in a large population. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/ajmg.a.63781 |
| الاتاحة: | https://doi.org/10.1002/ajmg.a.63781 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.63781 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.A1389D35 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/ajmg.a.63781 |
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