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 EFTUD2 (NM_004247.3) gene in the proband. Previous studies have reported that the variants in EFTUD2 gene were associated with Mandibulofacial Dysostosis with Microcephaly.
CONCLUSION
Patients with facial asymmetry, micrognathia, choanal atresia and microcephaly should be analyzed for variants in EFTUD2 gene. Next-generation sequencing techniques, such as whole-exome sequencing offer great promise to improve the understanding of etiologies of sporadic genetic diseases.
TY - JOUR
T1 - Whole-exome sequencing identified a variant in EFTUD2 gene in establishing a genetic diagnosis.
AU - Rengasamy Venugopalan,S,
AU - Farrow,E G,
AU - Lypka,M,
PY - 2017/02/25/accepted
PY - 2017/6/24/entrez
PY - 2017/6/24/pubmed
PY - 2018/6/30/medline
KW - EFTUD2
KW - Mandibulofacial Dysostosis
KW - microcephaly
KW - whole-exome sequencing
SP - 50
EP - 56
JF - Orthodontics & craniofacial research
JO - Orthod Craniofac Res
VL - 20 Suppl 1
N2 - 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 EFTUD2 (NM_004247.3) gene in the proband. Previous studies have reported that the variants in EFTUD2 gene were associated with Mandibulofacial Dysostosis with Microcephaly. CONCLUSION: Patients with facial asymmetry, micrognathia, choanal atresia and microcephaly should be analyzed for variants in EFTUD2 gene. Next-generation sequencing techniques, such as whole-exome sequencing offer great promise to improve the understanding of etiologies of sporadic genetic diseases.
SN - 1601-6343
UR - https://www.unboundmedicine.com/medline/citation/28643921/Whole_exome_sequencing_identified_a_variant_in_EFTUD2_gene_in_establishing_a_genetic_diagnosis_
DB - PRIME
DP - Unbound Medicine
ER -
