A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes

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  • Abu Bakar
  • Asmat Ullah
  • Nousheen Bibi
  • Hammal Khan
  • Ateeq ur Rahman
  • Wasim Ahmad
  • Bushra Khan

Polydactyly is a human inherited disorder caused by to anomalies in the genes involved in autopod development. The disorder segregates in both autosomal recessive and autosomal dominant form. Up till now, eleven genes causing non-syndromic polydactyly, have been identified. This includes ZNF141, GLI3, ZRS in LMBR1, MIPOL1, PITX1, IQCE, GLI1, FMA92A1, KIAA0825, STKLD1, and DACH1. In the present study, we have investigated a large consanguineous family of Pakistani origin segregating polydactyly in autosomal recessive pattern. Clinical examination of affected individuals revealed a non-syndromic form of the disorder. Genetic study based on homozygosity mapping and Sanger sequencing using DNA of the normal and affected individuals found a novel homozygous missense sequence variant [NM_005269.3: c.1133C > T, p.(Ser378Leu)] in the GLI1 located on human chromosome 12q13.3. In silico analysis of the identified variant showed a significant change in the secondary structure of the mutant protein that affects its function. Findings of the present study expand the mutation spectrum of the GLI1. In addition, the study will help in prevention of the disorder through carrier testing and bringing awareness among families affected with polydactyly.

Original languageEnglish
Article number104599
JournalEuropean Journal of Medical Genetics
Issue number10
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Masson SAS

    Research areas

  • A novel homozygous variant, GLI1, Homozygosity mapping, Polydactyly, Sanger sequencing

ID: 320649131