Experience with the targeted next-generation sequencing in the diagnosis of hereditary hypophosphatemic rickets
Journal of Pediatric Endocrinology and Metabolism, cilt.34, sa.5, ss.639-648, 2021 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 34 Sayı: 5
- Basım Tarihi: 2021
- Doi Numarası: 10.1515/jpem-2020-0624
- Dergi Adı: Journal of Pediatric Endocrinology and Metabolism
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
- Sayfa Sayıları: ss.639-648
- Anahtar Kelimeler: DMP13, ENPP1, Hypophosphatemic rickets, PHEX, SLC34A1, SLC34A3, Targeted next-generation sequencing gene panel
- Ankara Yıldırım Beyazıt Üniversitesi Adresli: Hayır
Özet
Objectives: Hereditary Hypophosphatemic Rickets (HHR) is a heterogeneous group of disorders characterized by hypophosphatemia. Although the X-linked dominant HHR is the most common form, the genetic etiology of HHR is variable. Recently, developed next-generation sequencing techniques may provide opportunities for making HHR diagnosis in a timely and efficient way. Methods: We investigated clinical and genetic features for 18 consecutive probands and their 17 affected family members with HHR. All patient's clinical and biochemical data were collected. We first analyzed a single gene with Nextgeneration sequencing if the patients have a strong clue for an individual gene. For the remaining cases, a Hypophosphatemic Rickets gene panel, including all known HHR genes by Next-generation sequencing, was employed. Results: We were able to diagnosis all of the consecutive 35 patients in our tertiary care center. We detected nine novel and 10 previously described variants in PHEX (9; 50%), SLC34A3 (3; 17%), ENPP1 (3; 17%), SLC34A1 (1; 5%), CLCN5 (1; 5%), and DMP1 (1; 5%). Conclusions: To delineate the etiology of HHR cases in a cost and time-efficient manner, we propose single gene analysis by next-generation sequencing if findings of patients indicate a strong clue for an individual gene. If that analysis is negative or for all other cases, a Next-generation Sequence gene panel, which includes all knownHHR genes, should be employed.