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

Research output: Contribution to journalJournal articlepeer-review

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A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes. / Bakar, Abu; Ullah, Asmat; Bibi, Nousheen; Khan, Hammal; Rahman, Ateeq ur; Ahmad, Wasim; Khan, Bushra.

In: European Journal of Medical Genetics, Vol. 65, No. 10, 104599, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Bakar, A, Ullah, A, Bibi, N, Khan, H, Rahman, AU, Ahmad, W & Khan, B 2022, 'A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes', European Journal of Medical Genetics, vol. 65, no. 10, 104599. https://doi.org/10.1016/j.ejmg.2022.104599

APA

Bakar, A., Ullah, A., Bibi, N., Khan, H., Rahman, A. U., Ahmad, W., & Khan, B. (2022). A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes. European Journal of Medical Genetics, 65(10), [104599]. https://doi.org/10.1016/j.ejmg.2022.104599

Vancouver

Bakar A, Ullah A, Bibi N, Khan H, Rahman AU, Ahmad W et al. A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes. European Journal of Medical Genetics. 2022;65(10). 104599. https://doi.org/10.1016/j.ejmg.2022.104599

Author

Bakar, Abu ; Ullah, Asmat ; Bibi, Nousheen ; Khan, Hammal ; Rahman, Ateeq ur ; Ahmad, Wasim ; Khan, Bushra. / A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes. In: European Journal of Medical Genetics. 2022 ; Vol. 65, No. 10.

Bibtex

@article{58d3bee52f6a440384e1de297e333579,
title = "A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes",
abstract = "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.",
keywords = "A novel homozygous variant, GLI1, Homozygosity mapping, Polydactyly, Sanger sequencing",
author = "Abu Bakar and Asmat Ullah and Nousheen Bibi and Hammal Khan and Rahman, {Ateeq ur} and Wasim Ahmad and Bushra Khan",
note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Masson SAS",
year = "2022",
doi = "10.1016/j.ejmg.2022.104599",
language = "English",
volume = "65",
journal = "European Journal of Medical Genetics",
issn = "1769-7212",
publisher = "Elsevier Masson",
number = "10",

}

RIS

TY - JOUR

T1 - A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes

AU - Bakar, Abu

AU - Ullah, Asmat

AU - Bibi, Nousheen

AU - Khan, Hammal

AU - Rahman, Ateeq ur

AU - Ahmad, Wasim

AU - Khan, Bushra

N1 - Publisher Copyright: © 2022 Elsevier Masson SAS

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - A novel homozygous variant

KW - GLI1

KW - Homozygosity mapping

KW - Polydactyly

KW - Sanger sequencing

U2 - 10.1016/j.ejmg.2022.104599

DO - 10.1016/j.ejmg.2022.104599

M3 - Journal article

C2 - 36067927

AN - SCOPUS:85137385603

VL - 65

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

SN - 1769-7212

IS - 10

M1 - 104599

ER -

ID: 320649131