Abstract:
Background Larsen syndrome (OMIM 150250) is an autosomal dominant syndrome caused by mutation in the FLNB gene. It is characterized by bilateral elbow dislocation, hip dislocation, knee dislocation, talipes equinovarus, and spatulate thumbs.
Objective To identify pathogenic mutations in a fetus with joint contracture indicated by intrauterine ultrasound, and provide genetic counseling and reproductive guidance.
Methods The genomic DNA (gDNA) extracted from the umbilical cord blood and peripheral blood of the parents and the femur muscle tissue of the fetus who admitted to the First Medical Center of Chinese PLA General Hospital in June 2015 were collected, then bioinformation analysis was performed. The candidate pathogenic variants were confirmed by Sanger sequencing in the family.
Results No abnormality was found in the medical history information of this family, the fetus was found to have contracture and fixation of bilateral elbow and knee joints, spatulate thumbs, contracture of bilateral distal interphalangeal joint, bilateral wrist joints extension contracture and talipes. Next generation sequencing panel analysis identified that the heterozygous variant in FLNB gene was c.565(E3)T＞C (p.189, W＞R) in the fetus, while the analysis resluts to parents and the second child were normal.
Conclusion Our study identifies that the pathogenicity locus is c.565(E3)T＞C (p.189, W＞R) by next generation sequencing panel, which provide useful information for genetic counseling and guidance of repregnancy.
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