التفاصيل البيبلوغرافية
| العنوان: |
Somatic Double Inactivation of NF1 Associated with NF1-Related Pectus Excavatum Deformity |
| المؤلفون: |
Cristina Chelleri, Marcello Scala, Patrizia De Marco, Vittorio Guerriero, Marzia Ognibene, Francesca Madia, Sara Guerrisi, Marco Di Duca, Michele Torre, Serena Tamburro, Paolo Scudieri, Gianluca Piccolo, Girolamo Mattioli, Francesca Buffelli, Paolo Uva, Diego Vozzi, Ezio Fulcheri, Pasquale Striano, Maria Cristina Diana, Federico Zara |
| بيانات النشر: |
Human Mutation |
| سنة النشر: |
2023 |
| المجموعة: |
Hindawi Publishing Corporation |
| الوصف: |
Neurofibromatosis type 1 (NF1) is a neurocutaneous genetic disorder with a broad spectrum of associated signs and symptoms, including skeletal anomalies. The association of NF1 with anterior chest wall deformities has been recently reported, especially the pectus excavatum (PE). Over the years, several authors have suggested loss of heterozygosity (LOH) as the possible pathogenic mechanism underlying the development of the typical NF1 skeletal features. Here, we report a NF1 patient with severe chest deformity and harboring the germline heterozygous pathogenic NF1 variant NM_001042492.3: c.4271delC p.(Ala1424Glufs∗4). Through next-generation sequencing (NGS), we investigated the affected cartilage from the PE deformity and identified the additional frameshift variant NM_001042492.3: c.2953delC p.(Gln985Lysfs∗7), occurring as a somatic NF1 second hit mutation. Exome sequencing confirmed the absence of additional variants of potential pathogenic relevance. Western blot analysis showed the absence of wild-type NF1 protein in the cartilage of the patient, consistent with a somatic double inactivation (SDI) of NF1. Taken together, our findings support the role of SDI in NF1-related PE, widening the spectrum of the pathophysiological mechanisms involved in NF1-related skeletal features. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
https://doi.org/10.1155/2023/3160653Test |
| DOI: |
10.1155/2023/3160653 |
| الإتاحة: |
https://doi.org/10.1155/2023/3160653Test |
| حقوق: |
Copyright © 2023 Cristina Chelleri et al. |
| رقم الانضمام: |
edsbas.12F4CD10 |
| قاعدة البيانات: |
BASE |
