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Identification of GLI1 and KIAA0825 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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137575/ https://www.ncbi.nlm.nih.gov/pubmed/37107627 http://dx.doi.org/10.3390/genes14040869 |
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author | Ahmad, Safeer Ali, Muhammad Zeeshan Muzammal, Muhammad Khan, Amjad Ullah Ikram, Muhammad Muurinen, Mari Hussain, Shabir Loid, Petra Khan, Muzammil Ahmad Mäkitie, Outi |
author_facet | Ahmad, Safeer Ali, Muhammad Zeeshan Muzammal, Muhammad Khan, Amjad Ullah Ikram, Muhammad Muurinen, Mari Hussain, Shabir Loid, Petra Khan, Muzammil Ahmad Mäkitie, Outi |
author_sort | Ahmad, Safeer |
collection | PubMed |
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 KIAA0825 (c.3572C>T: p.Pro1191Leu) in family A and a known nonsense variant in GLI1 (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 KIAA0825 and demonstrates the second case of a previously identified GLI1 variant with variable phenotypes. These findings facilitate genetic counseling in Pakistani families with a polydactyly-related phenotype. |
format | Online Article Text |
id | pubmed-10137575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101375752023-04-28 Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly Ahmad, Safeer Ali, Muhammad Zeeshan Muzammal, Muhammad Khan, Amjad Ullah Ikram, Muhammad Muurinen, Mari Hussain, Shabir Loid, Petra Khan, Muzammil Ahmad Mäkitie, Outi Genes (Basel) Article 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 KIAA0825 (c.3572C>T: p.Pro1191Leu) in family A and a known nonsense variant in GLI1 (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 KIAA0825 and demonstrates the second case of a previously identified GLI1 variant with variable phenotypes. These findings facilitate genetic counseling in Pakistani families with a polydactyly-related phenotype. MDPI 2023-04-05 /pmc/articles/PMC10137575/ /pubmed/37107627 http://dx.doi.org/10.3390/genes14040869 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ahmad, Safeer Ali, Muhammad Zeeshan Muzammal, Muhammad Khan, Amjad Ullah Ikram, Muhammad Muurinen, Mari Hussain, Shabir Loid, Petra Khan, Muzammil Ahmad Mäkitie, Outi Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly |
title | Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly |
title_full | Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly |
title_fullStr | Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly |
title_full_unstemmed | Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly |
title_short | Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly |
title_sort | identification of gli1 and kiaa0825 variants in two families with postaxial polydactyly |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137575/ https://www.ncbi.nlm.nih.gov/pubmed/37107627 http://dx.doi.org/10.3390/genes14040869 |
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