A novel frameshift variant in UBA2 causing split-hand/foot malformations in a Pakistani family

Asia Parveen; Muhammad Tariq; Sher Alam Khan; Naseebullah Kakar; Amina Arif; Naveed Wasif

doi:10.1038/s41439-023-00242-z

A novel frameshift variant in UBA2 causing split-hand/foot malformations in a Pakistani family

Hum Genome Var. 2023 May 23;10(1):16. doi: 10.1038/s41439-023-00242-z.

Authors

Asia Parveen^{1

2}, Muhammad Tariq³, Sher Alam Khan⁴, Naseebullah Kakar^{5

6}, Amina Arif¹, Naveed Wasif^{7

8}

Affiliations

¹ Faculty of Science and Technology, University of Central Punjab (UCP), Lahore, Pakistan.
² Department of Biochemistry Faculty of Life Sciences, Gulab Devi Educational Complex, Lahore, Pakistan.
³ Department of Medical Laboratory Technology, University College of Duba, University of Tabuk, Tabuk, Kingdom of Saudi Arabia.
⁴ Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, Pakistan.
⁵ Department of Biotechnology, BUITEMS, Quetta, Pakistan.
⁶ Institute of Human Genetics, University Hospital Schleswig-Holstein, Luebeck, Germany.
⁷ Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany. naveedwasif@gmail.com.
⁸ Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. naveedwasif@gmail.com.

Abstract

Split-hand/foot malformation (SHFM) shows diverse heterogeneity and manifests with reduced penetrance and variable expressivity. This study investigated the underlying genetic cause of a family segregating SHFM. Exome sequencing followed by Sanger sequencing identified a novel single nucleotide heterozygous variant (NC_000019.9 (NM_005499.3):c.1118del) in UBA2 cosegregating in the family in an autosomal dominant manner. Our findings conclude that reduced penetrance and variable expressivity are the two remarkable and unusual features of SHFM.