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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...

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Autores principales: Ahmad, Safeer, Ali, Muhammad Zeeshan, Muzammal, Muhammad, Khan, Amjad Ullah, Ikram, Muhammad, Muurinen, Mari, Hussain, Shabir, Loid, Petra, Khan, Muzammil Ahmad, Mäkitie, Outi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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