Abstract:

Objective: To conduct clinical and molecular genetic analysis in a Chinese family with familial polysyndactyly. Methods: A pregnant woman with fetal polysyndactyly was enrolled in this study, amniocentesis was performed at Quanzhou Women′s and Children′s Hospital for prenatal diagnosis at the gestational age of 24⁺⁵ weeks. Chromosomal karyotype analysis was performed to reveal fetal chromosomal abnormalities. Subsequently, whole exome sequencing (WES) was carried out to analyze sequence variations. Quantitative real time polymerase chain reaction(qPCR) was use to confirm the detected microdeletion/microduplication. Results: The fetal chromosome karyotype results elicited a normal karyotype result. However, WES demonstrated an 803.7 kb fragment duplication (seq[GRCh37]7q36.3(155865332_156669022)×3) in the 7q36.3 region in the fetus, which covering RNF32 and LMBR1 (exon 2 to exon 17). According to the American College of Medical Genetics and Genomics(ACMG) guidelines, the 7q36.3 duplication was interpreted as pathogenic copy number variants. The subsequent qPCR verification indicated that the duplication was inherited from the father who had similar clinical phenotype. Conclusions: Our findings further confirm that 7q36.3 microduplication is the genetic cause for fetal polysyndactyly, which may lead to triphalangeal thumb-polysyndactyly syndrome, LMBR1 may be the main effector gene.

Key words: Polydactyly, Syndactyly, Etiology diagnosis, Whole exome sequencing, Karyotype analysis, Prenatal diagnosis, Copy number variants