A Novel Homozygous Nonsense Variant in the DΥM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A Novel Homozygous Nonsense Variant in the DΥM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family. / Bakar, Abu; Shams, Sulaiman; Bibi, Nousheen; Ullah, Asmat; Ahmad, Wasim; Jelani, Musharraf; Muthaffar, Osama Yousef; Abdulkareem, Angham Abdulrhman; Abujamel, Turki S.; Haque, Absarul; Naseer, Muhammad Imran; Khan, Bushra.

In: Genes, Vol. 14, 510, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bakar, A, Shams, S, Bibi, N, Ullah, A, Ahmad, W, Jelani, M, Muthaffar, OY, Abdulkareem, AA, Abujamel, TS, Haque, A, Naseer, MI & Khan, B 2023, 'A Novel Homozygous Nonsense Variant in the DΥM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family', Genes, vol. 14, 510. https://doi.org/10.3390/genes14020510

APA

Bakar, A., Shams, S., Bibi, N., Ullah, A., Ahmad, W., Jelani, M., Muthaffar, O. Y., Abdulkareem, A. A., Abujamel, T. S., Haque, A., Naseer, M. I., & Khan, B. (2023). A Novel Homozygous Nonsense Variant in the DΥM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family. Genes, 14, [510]. https://doi.org/10.3390/genes14020510

Vancouver

Bakar A, Shams S, Bibi N, Ullah A, Ahmad W, Jelani M et al. A Novel Homozygous Nonsense Variant in the DΥM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family. Genes. 2023;14. 510. https://doi.org/10.3390/genes14020510

Author

Bakar, Abu ; Shams, Sulaiman ; Bibi, Nousheen ; Ullah, Asmat ; Ahmad, Wasim ; Jelani, Musharraf ; Muthaffar, Osama Yousef ; Abdulkareem, Angham Abdulrhman ; Abujamel, Turki S. ; Haque, Absarul ; Naseer, Muhammad Imran ; Khan, Bushra. / A Novel Homozygous Nonsense Variant in the DΥM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family. In: Genes. 2023 ; Vol. 14.

Bibtex

@article{02726722c1e3426eb343308c7e956111,
title = "A Novel Homozygous Nonsense Variant in the DΥM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family",
abstract = "(1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited. The family members were analyzed by polymerase chain reaction for homozygosity mapping using highly polymorphic microsatellite markers. Subsequent to linkage analysis, the coding exons and exon intron border of the DYM gene were amplified. The amplified products were then sent for Sanger sequencing. The structural effect of the pathogenic variant was analyzed by different bioinformatics tools. (3) Results: Homozygosity mapping revealed a 9 Mb homozygous region on chromosome 18q21.1 harboring DYM shared by all available affected individuals. Sanger sequencing of the coding exons and exon intron borders of the DYM gene revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T>A, p.(Leu402Ter)] in affected individuals. All the available unaffected individuals were either heterozygous or wild type for the identified variant. The identified mutation results in loss of protein stability and weekend interactions with other proteins making them pathogenic (4) Conclusions: This is the second nonsense mutation reported in a Pakistani population causing DMC. The study presented would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community.",
keywords = "Dyggve-Melchior-Clausen Syndrome, DYM gene, homozgosity mapping, non-sense variant, novel homozygous, sanger sequencing",
author = "Abu Bakar and Sulaiman Shams and Nousheen Bibi and Asmat Ullah and Wasim Ahmad and Musharraf Jelani and Muthaffar, {Osama Yousef} and Abdulkareem, {Angham Abdulrhman} and Abujamel, {Turki S.} and Absarul Haque and Naseer, {Muhammad Imran} and Bushra Khan",
note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",
year = "2023",
doi = "10.3390/genes14020510",
language = "English",
volume = "14",
journal = "Genes",
issn = "2073-4425",
publisher = "M D P I AG",

}

RIS

TY - JOUR

T1 - A Novel Homozygous Nonsense Variant in the DΥM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family

AU - Bakar, Abu

AU - Shams, Sulaiman

AU - Bibi, Nousheen

AU - Ullah, Asmat

AU - Ahmad, Wasim

AU - Jelani, Musharraf

AU - Muthaffar, Osama Yousef

AU - Abdulkareem, Angham Abdulrhman

AU - Abujamel, Turki S.

AU - Haque, Absarul

AU - Naseer, Muhammad Imran

AU - Khan, Bushra

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - (1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited. The family members were analyzed by polymerase chain reaction for homozygosity mapping using highly polymorphic microsatellite markers. Subsequent to linkage analysis, the coding exons and exon intron border of the DYM gene were amplified. The amplified products were then sent for Sanger sequencing. The structural effect of the pathogenic variant was analyzed by different bioinformatics tools. (3) Results: Homozygosity mapping revealed a 9 Mb homozygous region on chromosome 18q21.1 harboring DYM shared by all available affected individuals. Sanger sequencing of the coding exons and exon intron borders of the DYM gene revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T>A, p.(Leu402Ter)] in affected individuals. All the available unaffected individuals were either heterozygous or wild type for the identified variant. The identified mutation results in loss of protein stability and weekend interactions with other proteins making them pathogenic (4) Conclusions: This is the second nonsense mutation reported in a Pakistani population causing DMC. The study presented would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community.

AB - (1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited. The family members were analyzed by polymerase chain reaction for homozygosity mapping using highly polymorphic microsatellite markers. Subsequent to linkage analysis, the coding exons and exon intron border of the DYM gene were amplified. The amplified products were then sent for Sanger sequencing. The structural effect of the pathogenic variant was analyzed by different bioinformatics tools. (3) Results: Homozygosity mapping revealed a 9 Mb homozygous region on chromosome 18q21.1 harboring DYM shared by all available affected individuals. Sanger sequencing of the coding exons and exon intron borders of the DYM gene revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T>A, p.(Leu402Ter)] in affected individuals. All the available unaffected individuals were either heterozygous or wild type for the identified variant. The identified mutation results in loss of protein stability and weekend interactions with other proteins making them pathogenic (4) Conclusions: This is the second nonsense mutation reported in a Pakistani population causing DMC. The study presented would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community.

KW - Dyggve-Melchior-Clausen Syndrome

KW - DYM gene

KW - homozgosity mapping

KW - non-sense variant

KW - novel homozygous

KW - sanger sequencing

U2 - 10.3390/genes14020510

DO - 10.3390/genes14020510

M3 - Journal article

C2 - 36833437

AN - SCOPUS:85148862437

VL - 14

JO - Genes

JF - Genes

SN - 2073-4425

M1 - 510

ER -

ID: 339624011