Neurofibromatosis type 1: Expanded variant spectrum with multiplex ligation‐dependent probe amplification and genotype–phenotype correlation in 138 Turkish patients
| العنوان: | Neurofibromatosis type 1: Expanded variant spectrum with multiplex ligation‐dependent probe amplification and genotype–phenotype correlation in 138 Turkish patients |
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| المؤلفون: | Gozde Yesil, Nilay Güneş, Busra Kasap, Tiraje Celkan, Rejin Kebudi, Filiz Geyik, Beyhan Tüysüz |
| المساهمون: | YEŞİL, Gözde |
| المصدر: | Annals of Human Genetics. 85:155-165 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Pathology, medicine.medical_specialty, Neurofibromatosis 1, Adolescent, Turkey, Expanded variant spectrum with multiplex ligation-dependent probe amplification and genotype-phenotype correlation in 138 Turkish patients-, ANNALS OF HUMAN GENETICS, 2021 [Gunes N., YEŞİL G., Geyik F., Kasap B., Celkan T., Kebudi R., TÜYSÜZ B., -Neurofibromatosis type 1], Genotype phenotype, Correlation, Young Adult, 03 medical and health sciences, Age groups, Genetics, Humans, Medicine, In patient, Multiplex, Multiplex ligation-dependent probe amplification, Neurofibromatosis, Child, neoplasms, Genetic Association Studies, Genetics (clinical), Retrospective Studies, 030304 developmental biology, 0303 health sciences, business.industry, 030305 genetics & heredity, Infant, medicine.disease, Phenotype, eye diseases, nervous system diseases, Child, Preschool, population characteristics, Female, business, Multiplex Polymerase Chain Reaction |
| الوصف: | OBJECTIVE To investigate the variant spectrum and genotype-phenotype correlations in a Turkish cohort with Neurofibromatosis Type-1 (NF1). MATERIALS AND METHODS We retrospectively investigated the clinical and molecular data of 138 NF1 patients from 129 families who had been followed-up for a median of 3.9 (1.25-18.5) years. RESULTS NF1 sequencing revealed 73 different intragenic variants, 19 of which were novel. Seven large deletions were detected by multiplex ligation-dependent probe amplification (MLPA) analyses. The total detection rate of pathogenic NF1 variants was found to be 87.1%. Comparing age groups, cutaneous neurofibromas, freckling, and Lisch nodules were more prevalent in patients older than 12 years (p > .05). Optic glioma detected in 17.3% of the patients and was significantly more common before the age of 6 (p > .001). Other solid tumors developed in 5% of the patients. There was no genotype-phenotype correlation between patients with truncating and nontruncating variants. However, six out of seven patients with large deletions had significant developmental delay, one patient with the c.2970_2972delAAT (p.Met992del) variant had only typical pigmentary features, and another patient with the c.4267A > G (p.Lys1423Glu) variant had CALMs, freckling, neurofibromas, and Noonan-like phenotype. CONCLUSIONS We described 19 novel variants and seven large deletions in NF1. Applying MLPA assay in NF1 is useful in expanding the molecular diagnosis. Although very limited genotype-phenotype correlation has been reported in NF1, the fact that specific phenotypic findings were observed in our patients with large deletions and two intragenic variants supports the studies published recently. |
| تدمد: | 1469-1809 0003-4800 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::245de901af46dc132487b061e1be4b4fTest https://doi.org/10.1111/ahg.12422Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....245de901af46dc132487b061e1be4b4f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14691809 00034800 |
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