Intragenic multi-exon deletion in the FBN1 gene in a child with mildly dilated aortic sinus: a retrotransposal event.
Marfan syndrome is an autosomal dominant disorder affecting mainly the skeletal, ocular and cardiovascular systems. Most cases are caused by mutations in the fibrillin-1 gene (FBN1), although there are some reports on deletions involving FBN1 and other additional genes. We report a male patient who was first evaluated at 4 years of age. Echocardiogram showed a mildly dilated aortic sinus. He also had a history of muscular ventral septal defect which was closed spontaneously and trivial mitral regurgitation. Other phenotypic features include frontal bossing, anteverted ears, joint hyperlaxity, learning disability, skin striae, and height and weight in the >97th centile but no other diagnostic findings of MFS and does not fulfill the revised Ghent criteria. Chromosomal microarray analysis showed a deletion of approximately 36.8 kb at 15q21.1, which starts in intron 6 and ends in intron 9 and includes three FBN1 exons. Sequence analysis of the breakpoint region confirmed the deletion and revealed a concomitant insertion of a retrotransposon within the intron 6/intron 9 region. The intragenic deletion of exons 7-9 was likely the result of a retrotransposition event by a MAST2-SVA element mediated by repetitive sequences.
KK Research Laboratory, KK Women's and Children's Hospital, Singapore, Singapore.
Maggie
M
Brett
KK Research Laboratory, KK Women's and Children's Hospital, Singapore, Singapore.
George
G
Korovesis
Genetics Service, KK Women's and Children's Hospital, Singapore, Singapore.|Paediatrics Academic Clinical Programme, SingHealth/Duke-NUS Medical School, Singapore, Singapore.
Angeline H M
AHM
Lai
KK Research Laboratory, KK Women's and Children's Hospital, Singapore, Singapore.
Eileen C P
ECP
Lim
KK Research Laboratory, KK Women's and Children's Hospital, Singapore, Singapore.|Paediatrics Academic Clinical Programme, SingHealth/Duke-NUS Medical School, Singapore, Singapore.
Ene-Choo
EC
Tan
D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004108:Dilatation, Pathologic; D005091:Exons / Q000235:genetics*; D000071838:Fibrillin-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D017384:Sequence Deletion / Q000235:genetics*; D012850:Sinus of Valsalva / Q000002:abnormalities*
D000071838:Fibrillin-1