Premium
Whole‐exome sequencing identified a variant in EFTUD 2 gene in establishing a genetic diagnosis
Author(s) -
Rengasamy Venugopalan S.,
Farrow E. G.,
Lypka M.
Publication year - 2017
Publication title -
orthodontics and craniofacial research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 55
eISSN - 1601-6343
pISSN - 1601-6335
DOI - 10.1111/ocr.12150
Subject(s) - proband , exome sequencing , microcephaly , genetics , medicine , exome , biology , bioinformatics , gene , phenotype , mutation
Structured Abstract Objectives Craniofacial anomalies are complex and have an overlapping phenotype. Mandibulofacial Dysostosis and Oculo‐Auriculo‐Vertebral Spectrum are conditions that share common craniofacial phenotype and present a challenge in arriving at a diagnosis. In this report, we present a case of female proband who was given a differential diagnosis of Treacher Collins syndrome or Hemifacial Microsomia without certainty. Prior genetic testing reported negative for 22q deletion and FGFR screenings. The objective of this study was to demonstrate the critical role of whole‐exome sequencing in establishing a genetic diagnosis of the proband. Setting and Sample Population The participants were 14½‐year‐old affected female proband/parent trio. Materials and Methods Proband/parent trio were enrolled in the study. Surgical tissue sample from the proband and parental blood samples were collected and prepared for whole‐exome sequencing. Illumina HiSeq 2500 instrument was used for sequencing (125 nucleotide reads/84X coverage). Analyses of variants were performed using custom‐developed software, RUNES and VIKING . Results Variant analyses following whole‐exome sequencing identified a heterozygous de novo pathogenic variant, c.259C>T (p.Gln87*), in EFTUD 2 ( NM_004247.3 ) gene in the proband. Previous studies have reported that the variants in EFTUD 2 gene were associated with Mandibulofacial Dysostosis with Microcephaly . Conclusion Patients with facial asymmetry, micrognathia, choanal atresia and microcephaly should be analyzed for variants in EFTUD 2 gene. Next‐generation sequencing techniques, such as whole‐exome sequencing offer great promise to improve the understanding of etiologies of sporadic genetic diseases.