Exome Sequencing and High-Density Microarray Testing in Monozygotic Twin Pairs Discordant for Features of VACTERL Association

Molecular Syndromology

NISC Comparative Sequencing Program¹  S.C. Chandrasekharappa¹  J.C. Mullikin¹  D.E. Pineda-Alvarez¹  A. Kamat¹  F.X. Donovan¹  S.-K. Hong¹  E. Roessler¹  D.W. Hadley¹  B.D. Solomon¹  N.F. Hansen¹ 

[1] aMedical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., USA

关键词: Exome sequencing;    Twin studies;    VACTERL association;   

DOI  :  10.1159/000345406

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

Exome sequencing offers an efficient and affordable method to interrogate genetic factors involved in human disease. Performing exome sequencing of monozygotic twins discordant for VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities) association-type congenital malformations was hypothesized to potentially reveal discordant variants that could demonstrate disease cause(s). After demonstrating monozygosity, we applied high-density microarrays and exome sequencing to 2 twin pairs in which 1 twin had features of VACTERL association while the other was phenotypically normal (demonstrated through comprehensive clinical and radiological evaluation). No obvious discordant genotypic results were found that would explain phenotypic discordance. We conclude that VACTERL association is a complex disease, and while performing microarray analysis and exome sequencing on phenotypically discordant monozygotic twins may hypothetically reveal genetic causes of disorders, challenges remain in applying these methods in this circumstance.

【 授权许可】

Unknown