A novel missense variant in
Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Rahimian, Mouness [verfasserIn] Askari, Masomeh [verfasserIn] Salehi, Najmeh [verfasserIn] Riccio, Andrea [verfasserIn] Jaafarinia, Mojtaba [verfasserIn] Almadani, Navid [verfasserIn] Totonchi, Mehdi [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2023 |
|---|
| Schlagwörter: |
|---|
| Übergeordnetes Werk: |
Enthalten in: Taiwanese journal of obstetrics and gynecology - Singapore : Elsevier, 2004, 62, Seite 830-837 |
|---|---|
| Übergeordnetes Werk: |
volume:62 ; pages:830-837 |
| DOI / URN: |
10.1016/j.tjog.2023.03.015 |
|---|
| Katalog-ID: |
ELV065826604 |
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| 245 | 1 | 0 | |a A novel missense variant in |
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| 520 | |a Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. | ||
| 650 | 4 | |a Centrosomine | |
| 650 | 4 | |a WES | |
| 650 | 4 | |a Spindle checkpoint | |
| 650 | 4 | |a EB1/MAPRE1 | |
| 650 | 4 | |a Spermatogenesis | |
| 700 | 1 | |a Askari, Masomeh |e verfasserin |4 aut | |
| 700 | 1 | |a Salehi, Najmeh |e verfasserin |4 aut | |
| 700 | 1 | |a Riccio, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Jaafarinia, Mojtaba |e verfasserin |4 aut | |
| 700 | 1 | |a Almadani, Navid |e verfasserin |4 aut | |
| 700 | 1 | |a Totonchi, Mehdi |e verfasserin |4 aut | |
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10.1016/j.tjog.2023.03.015 doi (DE-627)ELV065826604 (ELSEVIER)S1028-4559(23)00239-5 DE-627 ger DE-627 rda eng 610 VZ 44.92 bkl Rahimian, Mouness verfasserin aut A novel missense variant in 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. Centrosomine WES Spindle checkpoint EB1/MAPRE1 Spermatogenesis Askari, Masomeh verfasserin aut Salehi, Najmeh verfasserin aut Riccio, Andrea verfasserin aut Jaafarinia, Mojtaba verfasserin aut Almadani, Navid verfasserin aut Totonchi, Mehdi verfasserin aut Enthalten in Taiwanese journal of obstetrics and gynecology Singapore : Elsevier, 2004 62, Seite 830-837 Online-Ressource (DE-627)500021422 (DE-600)2202946-1 (DE-576)272712795 1875-6263 nnns volume:62 pages:830-837 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_2014 GBV_ILN_2068 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.92 Gynäkologie VZ AR 62 830-837 |
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10.1016/j.tjog.2023.03.015 doi (DE-627)ELV065826604 (ELSEVIER)S1028-4559(23)00239-5 DE-627 ger DE-627 rda eng 610 VZ 44.92 bkl Rahimian, Mouness verfasserin aut A novel missense variant in 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. Centrosomine WES Spindle checkpoint EB1/MAPRE1 Spermatogenesis Askari, Masomeh verfasserin aut Salehi, Najmeh verfasserin aut Riccio, Andrea verfasserin aut Jaafarinia, Mojtaba verfasserin aut Almadani, Navid verfasserin aut Totonchi, Mehdi verfasserin aut Enthalten in Taiwanese journal of obstetrics and gynecology Singapore : Elsevier, 2004 62, Seite 830-837 Online-Ressource (DE-627)500021422 (DE-600)2202946-1 (DE-576)272712795 1875-6263 nnns volume:62 pages:830-837 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_2014 GBV_ILN_2068 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.92 Gynäkologie VZ AR 62 830-837 |
| allfields_unstemmed |
10.1016/j.tjog.2023.03.015 doi (DE-627)ELV065826604 (ELSEVIER)S1028-4559(23)00239-5 DE-627 ger DE-627 rda eng 610 VZ 44.92 bkl Rahimian, Mouness verfasserin aut A novel missense variant in 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. Centrosomine WES Spindle checkpoint EB1/MAPRE1 Spermatogenesis Askari, Masomeh verfasserin aut Salehi, Najmeh verfasserin aut Riccio, Andrea verfasserin aut Jaafarinia, Mojtaba verfasserin aut Almadani, Navid verfasserin aut Totonchi, Mehdi verfasserin aut Enthalten in Taiwanese journal of obstetrics and gynecology Singapore : Elsevier, 2004 62, Seite 830-837 Online-Ressource (DE-627)500021422 (DE-600)2202946-1 (DE-576)272712795 1875-6263 nnns volume:62 pages:830-837 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_2014 GBV_ILN_2068 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.92 Gynäkologie VZ AR 62 830-837 |
| allfieldsGer |
10.1016/j.tjog.2023.03.015 doi (DE-627)ELV065826604 (ELSEVIER)S1028-4559(23)00239-5 DE-627 ger DE-627 rda eng 610 VZ 44.92 bkl Rahimian, Mouness verfasserin aut A novel missense variant in 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. Centrosomine WES Spindle checkpoint EB1/MAPRE1 Spermatogenesis Askari, Masomeh verfasserin aut Salehi, Najmeh verfasserin aut Riccio, Andrea verfasserin aut Jaafarinia, Mojtaba verfasserin aut Almadani, Navid verfasserin aut Totonchi, Mehdi verfasserin aut Enthalten in Taiwanese journal of obstetrics and gynecology Singapore : Elsevier, 2004 62, Seite 830-837 Online-Ressource (DE-627)500021422 (DE-600)2202946-1 (DE-576)272712795 1875-6263 nnns volume:62 pages:830-837 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_2014 GBV_ILN_2068 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.92 Gynäkologie VZ AR 62 830-837 |
| allfieldsSound |
10.1016/j.tjog.2023.03.015 doi (DE-627)ELV065826604 (ELSEVIER)S1028-4559(23)00239-5 DE-627 ger DE-627 rda eng 610 VZ 44.92 bkl Rahimian, Mouness verfasserin aut A novel missense variant in 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. Centrosomine WES Spindle checkpoint EB1/MAPRE1 Spermatogenesis Askari, Masomeh verfasserin aut Salehi, Najmeh verfasserin aut Riccio, Andrea verfasserin aut Jaafarinia, Mojtaba verfasserin aut Almadani, Navid verfasserin aut Totonchi, Mehdi verfasserin aut Enthalten in Taiwanese journal of obstetrics and gynecology Singapore : Elsevier, 2004 62, Seite 830-837 Online-Ressource (DE-627)500021422 (DE-600)2202946-1 (DE-576)272712795 1875-6263 nnns volume:62 pages:830-837 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_2014 GBV_ILN_2068 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.92 Gynäkologie VZ AR 62 830-837 |
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englisch |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">ELV065826604</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20231126093038.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">231126s2023 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.tjog.2023.03.015</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV065826604</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S1028-4559(23)00239-5</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.92</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Rahimian, Mouness</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">A novel missense variant in</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. 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| author |
Rahimian, Mouness |
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Rahimian, Mouness ddc 610 bkl 44.92 misc Centrosomine misc WES misc Spindle checkpoint misc EB1/MAPRE1 misc Spermatogenesis A novel missense variant in |
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610 VZ 44.92 bkl A novel missense variant in Centrosomine WES Spindle checkpoint EB1/MAPRE1 Spermatogenesis |
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ddc 610 bkl 44.92 misc Centrosomine misc WES misc Spindle checkpoint misc EB1/MAPRE1 misc Spermatogenesis |
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ddc 610 bkl 44.92 misc Centrosomine misc WES misc Spindle checkpoint misc EB1/MAPRE1 misc Spermatogenesis |
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ddc 610 bkl 44.92 misc Centrosomine misc WES misc Spindle checkpoint misc EB1/MAPRE1 misc Spermatogenesis |
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A novel missense variant in |
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Rahimian, Mouness Askari, Masomeh Salehi, Najmeh Riccio, Andrea Jaafarinia, Mojtaba Almadani, Navid Totonchi, Mehdi |
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a novel missense variant in |
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A novel missense variant in |
| abstract |
Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. |
| abstractGer |
Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. |
| abstract_unstemmed |
Objective: The most severe type of male infertility is non-obstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis, affecting 10%–20% of infertile men with azoospermia. Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. In silico structural predictions and gene expression data indicate a potential role of the CDK5RAP2 variant in causing defective centrosomic maturation during spermatogenesis. |
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| title_short |
A novel missense variant in |
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Askari, Masomeh Salehi, Najmeh Riccio, Andrea Jaafarinia, Mojtaba Almadani, Navid Totonchi, Mehdi |
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Genetic studies have identified dozens of NOA genes. The main aim of the present study is to identify a novel monogenic mutation that may cause NOA.Materials and methods: We studied the pedigree of a consanguineous family with three NOA and one fertile brother by a family-based exome-sequencing, segregation analysis, insilico protein modeling and single-cell RNA sequencing data analysis.Results: Bioinformatics analysis followed by sanger sequencing revealed that three NOA brothers were homozygous for a rare missense variant in Cyclin Dependent Kinase Regulatory Subunit Associated Protein 2 (Centrosomin) CDK5RAP2 (NM_018249:exon26:c.A4003T:p.R1335W, rs761196443). Protein modeling demonstrated that CDK5RAP2, Arg1335Trp resided nearby the Microtubule Associated Protein RP/EB Family Member 1 (EB1/MAPRE1) interaction site. As a consequence of the R1335W mutation, the positively charged Arginine was replaced by to the hydrophobic tryptophan residue, possibly leading to local instability in the structure and perturbation in the CDK5RAP2-MAPRE1 interaction.Conclusion: Our study reports a novel missense variant of CDK5RAP2 that segregates in homozygosity with male infertility and NOA in a consanguineous family. 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