Identification of <i>GLI1</i> and <i>KIAA0825</i> Variants in Two Families with Postaxial Polydactyly
Polydactyly is a rare autosomal dominant or recessive appendicular patterning defect of the hands and feet, phenotypically characterized by the duplication of digits. Postaxial polydactyly (PAP) is the most common form and includes two main types: PAP type A (PAPA) and PAP type B (PAPB). Type A invo...
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MDPI AG
2023-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/4/869 |
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| author | Safeer Ahmad Muhammad Zeeshan Ali Muhammad Muzammal Amjad Ullah Khan Muhammad Ikram Mari Muurinen Shabir Hussain Petra Loid Muzammil Ahmad Khan Outi Mäkitie |
| author_facet | Safeer Ahmad Muhammad Zeeshan Ali Muhammad Muzammal Amjad Ullah Khan Muhammad Ikram Mari Muurinen Shabir Hussain Petra Loid Muzammil Ahmad Khan Outi Mäkitie |
| author_sort | Safeer Ahmad |
| collection | DOAJ |
| description | Polydactyly is a rare autosomal dominant or recessive appendicular patterning defect of the hands and feet, phenotypically characterized by the duplication of digits. Postaxial polydactyly (PAP) is the most common form and includes two main types: PAP type A (PAPA) and PAP type B (PAPB). Type A involves a well-established extra digit articulated with the fifth or sixth metacarpal, while type B presents a rudimentary or poorly developed superfluous digit. Pathogenic variants in several genes have been identified in isolated and syndromic forms of polydactyly. The current study presents two Pakistani families with autosomal recessive PAPA with intra- and inter-familial phenotype variability. Whole-exome sequencing and Sanger analysis revealed a novel missense variant in <i>KIAA0825</i> (c.3572C>T: p.Pro1191Leu) in family A and a known nonsense variant in <i>GLI1</i> (c.337C>T: p.Arg113*) in family B. In silico studies of mutant KIAA0825 and GLI1 proteins revealed considerable structural and interactional modifications that suggest an abnormal function of the proteins leading to the disease phenotype. The present study broadens the mutational spectrum of <i>KIAA0825</i> and demonstrates the second case of a previously identified <i>GLI1</i> variant with variable phenotypes. These findings facilitate genetic counseling in Pakistani families with a polydactyly-related phenotype. |
| first_indexed | 2024-03-11T04:58:44Z |
| format | Article |
| id | doaj.art-1f55b4d719bd4f59ae5a025b1a930381 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T04:58:44Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-1f55b4d719bd4f59ae5a025b1a9303812023-11-17T19:23:41ZengMDPI AGGenes2073-44252023-04-0114486910.3390/genes14040869Identification of <i>GLI1</i> and <i>KIAA0825</i> Variants in Two Families with Postaxial PolydactylySafeer Ahmad0Muhammad Zeeshan Ali1Muhammad Muzammal2Amjad Ullah Khan3Muhammad Ikram4Mari Muurinen5Shabir Hussain6Petra Loid7Muzammil Ahmad Khan8Outi Mäkitie9Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanGomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanGomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanGomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanGomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandGomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandPolydactyly is a rare autosomal dominant or recessive appendicular patterning defect of the hands and feet, phenotypically characterized by the duplication of digits. Postaxial polydactyly (PAP) is the most common form and includes two main types: PAP type A (PAPA) and PAP type B (PAPB). Type A involves a well-established extra digit articulated with the fifth or sixth metacarpal, while type B presents a rudimentary or poorly developed superfluous digit. Pathogenic variants in several genes have been identified in isolated and syndromic forms of polydactyly. The current study presents two Pakistani families with autosomal recessive PAPA with intra- and inter-familial phenotype variability. Whole-exome sequencing and Sanger analysis revealed a novel missense variant in <i>KIAA0825</i> (c.3572C>T: p.Pro1191Leu) in family A and a known nonsense variant in <i>GLI1</i> (c.337C>T: p.Arg113*) in family B. In silico studies of mutant KIAA0825 and GLI1 proteins revealed considerable structural and interactional modifications that suggest an abnormal function of the proteins leading to the disease phenotype. The present study broadens the mutational spectrum of <i>KIAA0825</i> and demonstrates the second case of a previously identified <i>GLI1</i> variant with variable phenotypes. These findings facilitate genetic counseling in Pakistani families with a polydactyly-related phenotype.https://www.mdpi.com/2073-4425/14/4/869polydactyly<i>KIAA0825</i><i>GLI1</i>Pakistani |
| spellingShingle | Safeer Ahmad Muhammad Zeeshan Ali Muhammad Muzammal Amjad Ullah Khan Muhammad Ikram Mari Muurinen Shabir Hussain Petra Loid Muzammil Ahmad Khan Outi Mäkitie Identification of <i>GLI1</i> and <i>KIAA0825</i> Variants in Two Families with Postaxial Polydactyly Genes polydactyly <i>KIAA0825</i> <i>GLI1</i> Pakistani |
| title | Identification of <i>GLI1</i> and <i>KIAA0825</i> Variants in Two Families with Postaxial Polydactyly |
| title_full | Identification of <i>GLI1</i> and <i>KIAA0825</i> Variants in Two Families with Postaxial Polydactyly |
| title_fullStr | Identification of <i>GLI1</i> and <i>KIAA0825</i> Variants in Two Families with Postaxial Polydactyly |
| title_full_unstemmed | Identification of <i>GLI1</i> and <i>KIAA0825</i> Variants in Two Families with Postaxial Polydactyly |
| title_short | Identification of <i>GLI1</i> and <i>KIAA0825</i> Variants in Two Families with Postaxial Polydactyly |
| title_sort | identification of i gli1 i and i kiaa0825 i variants in two families with postaxial polydactyly |
| topic | polydactyly <i>KIAA0825</i> <i>GLI1</i> Pakistani |
| url | https://www.mdpi.com/2073-4425/14/4/869 |
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