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Molecular Diagnosis of Craniosynostosis Using Targeted Next-Generation Sequencing

 Jihoon G Yoon  ;  Hyung Min Hahn  ;  Sungkyoung Choi  ;  Soo Jung Kim  ;  Sowon Aum  ;  Jung Woo Yu  ;  Eun Kyung Park  ;  Kyu Won Shim  ;  Min Goo Lee  ;  Yong Oock Kim 
 NEUROSURGERY, Vol.87(2) : 294-302, 2020-08 
Journal Title
Issue Date
Chromosomal abnormalities ; Congenital anomaly ; Craniosynostosis ; Genetic diagnosis ; Massively parallel sequencing
Background: Genetic factors play an important role in the pathogenesis of craniosynostosis (CRS). However, the molecular diagnosis of CRS in clinical practice is limited because of its heterogeneous etiology.

Objective: To investigate the genomic landscape of CRS in a Korean cohort and also to establish a practical diagnostic workflow by applying targeted panel sequencing.

Methods: We designed a customized panel covering 34 CRS-related genes using in-solution hybrid capture method. We enrolled 110 unrelated Korean patients with CRS, including 40 syndromic and 70 nonsyndromic cases. A diagnostic pipeline was established by combining in-depth clinical reviews and multiple bioinformatics tools for analyzing single-nucleotide variants (SNV)s and copy number variants (CNV)s.

Results: The diagnostic yield of the targeted panel was 30.0% (33/110). Twenty-five patients (22.7%) had causal genetic variations resulting from SNVs or indels in 9 target genes (TWIST1, FGFR3, TCF12, ERF, FGFR2, ALPL, EFNB1, FBN1, and SKI, in order of frequency). CNV analysis identified 8 (7.3%) additional patients with chromosomal abnormalities involving 1p32.3p31.3, 7p21.1, 10q26, 15q21.3, 16p11.2, and 17p13.3 regions; these cases mostly presented with syndromic clinical features.

Conclusion: The present study shows the wide genomic landscape of CRS, revealing various genetic factors for CRS pathogenesis. In addition, the results demonstrate that an efficient diagnostic workup using target panel sequencing provides great clinical utility in the molecular diagnosis of CRS.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Soo Jung(김수정)
Kim, Yong Oock(김용욱) ORCID logo https://orcid.org/0000-0002-3756-4809
Park, Eun Kyung(박은경)
Shim, Kyu Won(심규원) ORCID logo https://orcid.org/0000-0002-9441-7354
Yoon, Jihoon G.(윤지훈) ORCID logo https://orcid.org/0000-0002-4401-7803
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
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