AUTHOR=Fan Lihong , Jin Pengzhen , Qian Yeqing , Shen Guosong , Shen Xueping , Dong Minyue 

TITLE=Case Report: Prenatal Diagnosis of Postaxial Polydactyly With Bi-Allelic Variants in Smoothened (SMO)

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.887082

DOI=10.3389/fgene.2022.887082

ISSN=1664-8021

ABSTRACT=<p>Postaxial polydactyly is a common congenital malformation which involves complex genetic factors. This retrospective study analyzed the cytogenetic and molecular results of a Chinese fetus diagnosed with postaxial polydactyly of all four limbs. Fetal karyotyping and chromosomal microarray analysis (CMA) did not find any abnormality while trio whole-exome sequencing (trio-WES) identified bi-allelic variants in <ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/gene/6608" xmlns:xlink="http://www.w3.org/1999/xlink">smoothened</ext-link> (<italic>SMO</italic>) and (NM_005631.5: c.1219C &gt; G, <ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/protein/NP_005622.1" xmlns:xlink="http://www.w3.org/1999/xlink">NP_005622.1</ext-link>: p. Pro407Ala, and <ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/nuccore/NM_005631.5" xmlns:xlink="http://www.w3.org/1999/xlink">NM_005631.5</ext-link>: c.1619C &gt; T, <ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/protein/NP_005622.1" xmlns:xlink="http://www.w3.org/1999/xlink">NP_005622.1</ext-link>: p. Ala540Val). Sanger sequencing validated these variants. The mutations are highly conserved across multiple species. In-depth bioinformatics analysis and familial co-segregation implied the compound heterozygous variants as the likely cause of postaxial polydactyly in this fetus. Our findings provided the basis for genetic counseling and will contribute to a better understanding of the complex genetic mechanism that underlies postaxial polydactyly.</p>