Identification of nonfunctional PABPC1L causing oocyte maturation abnormalities and early embryonic arrest in female primary infertility
In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed n...
Source: Clinical Genetics - September 19, 2023 Category: Genetics & Stem Cells Authors: Xiang Wang Ruixi Zhou Xiaowei Lu Siyu Dai Mohan Liu Chuan Jiang Yanting Yang Ying Shen Yan Wang Hanmin Liu Source Type: research
Identification of nonfunctional PABPC1L causing oocyte maturation abnormalities and early embryonic arrest in female primary infertility
In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed n...
Source: Clinical Genetics - September 19, 2023 Category: Genetics & Stem Cells Authors: Xiang Wang Ruixi Zhou Xiaowei Lu Siyu Dai Mohan Liu Chuan Jiang Yanting Yang Ying Shen Yan Wang Hanmin Liu Source Type: research
Novel MEIOB pathogenic variants including a homozygous non-canonical splicing variant, cause meiotic arrest and human non-obstructive azoospermia
In this study, we identified novel compound heterozygous MEIOB variants (c.814C > T: p.R272X and c.976G > A: p.A326T) and a previously undescribed homozygous non-canonical splicing variant of MEIOB (c.528 + 3A > C) in two NOA-affected individuals from two irrelevant Chinese families. MEIOB missense variant (p.A326T) significantly reduced protein abundance and nonsense variant (p.R272X) produced a truncated protein. Both of two variants impaired the MEIOB-SPATA22 interaction. The MEIOB non-canonical splicing variant resulted in whole Exon 6 skipping by minigene assay, which was predicted to produce a frameshift tru...
Source: Clinical Genetics - September 16, 2023 Category: Genetics & Stem Cells Authors: Xiaoyu Zhu Kaiqin Hu Huiru Cheng Huan Wu Kuokuo Li Yang Gao Mingrong Lv Chuan Xu Hao Geng Qunshan Shen Yunxia Cao Xiaojin He Dongdong Tang Rui Guo Source Type: research
Novel MEIOB pathogenic variants including a homozygous non-canonical splicing variant, cause meiotic arrest and human non-obstructive azoospermia
In this study, we identified novel compound heterozygous MEIOB variants (c.814C > T: p.R272X and c.976G > A: p.A326T) and a previously undescribed homozygous non-canonical splicing variant of MEIOB (c.528 + 3A > C) in two NOA-affected individuals from two irrelevant Chinese families. MEIOB missense variant (p.A326T) significantly reduced protein abundance and nonsense variant (p.R272X) produced a truncated protein. Both of two variants impaired the MEIOB-SPATA22 interaction. The MEIOB non-canonical splicing variant resulted in whole Exon 6 skipping by minigene assay, which was predicted to produce a frameshift tru...
Source: Clinical Genetics - September 16, 2023 Category: Genetics & Stem Cells Authors: Xiaoyu Zhu Kaiqin Hu Huiru Cheng Huan Wu Kuokuo Li Yang Gao Mingrong Lv Chuan Xu Hao Geng Qunshan Shen Yunxia Cao Xiaojin He Dongdong Tang Rui Guo Source Type: research
Prospects and challenges of CRISPR/Cas9 gene-editing technology in cancer research
Clin Genet. 2023 Sep 14. doi: 10.1111/cge.14424. Online ahead of print.ABSTRACTCancer, one of the leading causes of death, usually commences and progresses as a result of a series of gene mutations and dysregulation of expression. With the development of clustered regularly interspaced palindromic repeat (CRISPR)/Cas9 gene-editing technology, it is possible to edit and then decode the functions of cancer-related gene mutations, markedly advance the research of biological mechanisms and treatment of cancer. This review summarizes the mechanism and development of CRISPR/Cas9 gene-editing technology in recent years and descri...
Source: Clinical Genetics - September 14, 2023 Category: Genetics & Stem Cells Authors: Li Ning Jiahui Xi Yin Zi Min Chen Qingjian Zou Xiaoqing Zhou Chengcheng Tang Source Type: research
Prospects and challenges of CRISPR/Cas9 gene-editing technology in cancer research
Clin Genet. 2023 Sep 14. doi: 10.1111/cge.14424. Online ahead of print.ABSTRACTCancer, one of the leading causes of death, usually commences and progresses as a result of a series of gene mutations and dysregulation of expression. With the development of clustered regularly interspaced palindromic repeat (CRISPR)/Cas9 gene-editing technology, it is possible to edit and then decode the functions of cancer-related gene mutations, markedly advance the research of biological mechanisms and treatment of cancer. This review summarizes the mechanism and development of CRISPR/Cas9 gene-editing technology in recent years and descri...
Source: Clinical Genetics - September 14, 2023 Category: Genetics & Stem Cells Authors: Li Ning Jiahui Xi Yin Zi Min Chen Qingjian Zou Xiaoqing Zhou Chengcheng Tang Source Type: research
Prospects and challenges of CRISPR/Cas9 gene-editing technology in cancer research
Clin Genet. 2023 Sep 14. doi: 10.1111/cge.14424. Online ahead of print.ABSTRACTCancer, one of the leading causes of death, usually commences and progresses as a result of a series of gene mutations and dysregulation of expression. With the development of clustered regularly interspaced palindromic repeat (CRISPR)/Cas9 gene-editing technology, it is possible to edit and then decode the functions of cancer-related gene mutations, markedly advance the research of biological mechanisms and treatment of cancer. This review summarizes the mechanism and development of CRISPR/Cas9 gene-editing technology in recent years and descri...
Source: Clinical Genetics - September 14, 2023 Category: Genetics & Stem Cells Authors: Li Ning Jiahui Xi Yin Zi Min Chen Qingjian Zou Xiaoqing Zhou Chengcheng Tang Source Type: research
Spectrum of variants in a large Chinese Gitelman syndrome cohort
Clin Genet. 2023 Sep 13. doi: 10.1111/cge.14422. Online ahead of print.ABSTRACTGitelman syndrome (GS) is caused by SLC12A3 biallelic variants. A previous study showed that large rearrangements (LRGs) of SLC12A3 accounted for the low sensitivity of genetic testing. However, a systematic screening for LRGs in Chinese GS patients is lacking. Massively parallel sequencing (MPS) and multiplex ligation-dependent probe amplification (MLPA) were performed to sequence the genomic DNA of patients with clinically diagnosed GS. Of 165 index cases, MPS identified 151 cases with two or more affected alleles and 14 cases with one variant...
Source: Clinical Genetics - September 13, 2023 Category: Genetics & Stem Cells Authors: Lijun Mou Mengyue Tang Lina Zhu Wanbing Lin Ying Gu Source Type: research
Lamb-Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency
In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to SOX5 haploinsufficiency.PMID:37702321 | DOI:10.1111/cge.14423 (Source: Clinical Genetics)
Source: Clinical Genetics - September 13, 2023 Category: Genetics & Stem Cells Authors: Jair Tenorio-Castano Ángela Sánchez-Algaba Gómez M ónica Coronado Pilar Rodr íguez-Martín Alejandro Parra Patricia Pascual Mario Cazalla Natalia Gallego Pedro Arias Aixa V Morales Juli án Nevado Pablo Lapunzina Source Type: research
Spectrum of variants in a large Chinese Gitelman syndrome cohort
Clin Genet. 2023 Sep 13. doi: 10.1111/cge.14422. Online ahead of print.ABSTRACTGitelman syndrome (GS) is caused by SLC12A3 biallelic variants. A previous study showed that large rearrangements (LRGs) of SLC12A3 accounted for the low sensitivity of genetic testing. However, a systematic screening for LRGs in Chinese GS patients is lacking. Massively parallel sequencing (MPS) and multiplex ligation-dependent probe amplification (MLPA) were performed to sequence the genomic DNA of patients with clinically diagnosed GS. Of 165 index cases, MPS identified 151 cases with two or more affected alleles and 14 cases with one variant...
Source: Clinical Genetics - September 13, 2023 Category: Genetics & Stem Cells Authors: Lijun Mou Mengyue Tang Lina Zhu Wanbing Lin Ying Gu Source Type: research
Lamb-Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency
In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to SOX5 haploinsufficiency.PMID:37702321 | DOI:10.1111/cge.14423 (Source: Clinical Genetics)
Source: Clinical Genetics - September 13, 2023 Category: Genetics & Stem Cells Authors: Jair Tenorio-Castano Ángela Sánchez-Algaba Gómez M ónica Coronado Pilar Rodr íguez-Martín Alejandro Parra Patricia Pascual Mario Cazalla Natalia Gallego Pedro Arias Aixa V Morales Juli án Nevado Pablo Lapunzina Source Type: research
Delineating the phenotype of PNPLA8-related mitochondriopathies
Clin Genet. 2023 Sep 6. doi: 10.1111/cge.14421. Online ahead of print.ABSTRACTPathogenic variants in PNPLA8 have been described either with congenital onset displaying congenital microcephaly, early onset epileptic encephalopathy and early lethality or childhood neurodegeneration with progressive microcephaly. Moreover, a phenotype comprising adulthood onset cerebellar ataxia and peripheral neuropathy was also reported. To our knowledge, only six patients with biallelic variants in PNPLA8 have been reported so far. Here, we report the clinical and molecular characterizations of three additional patients in whom exome seque...
Source: Clinical Genetics - September 6, 2023 Category: Genetics & Stem Cells Authors: Mohamed S Abdel-Hamid Ghada M H Abdel-Salam Sherif F Abdel-Ghafar Maha S Zaki Source Type: research
Delineating the phenotype of PNPLA8-related mitochondriopathies
Clin Genet. 2023 Sep 6. doi: 10.1111/cge.14421. Online ahead of print.ABSTRACTPathogenic variants in PNPLA8 have been described either with congenital onset displaying congenital microcephaly, early onset epileptic encephalopathy and early lethality or childhood neurodegeneration with progressive microcephaly. Moreover, a phenotype comprising adulthood onset cerebellar ataxia and peripheral neuropathy was also reported. To our knowledge, only six patients with biallelic variants in PNPLA8 have been reported so far. Here, we report the clinical and molecular characterizations of three additional patients in whom exome seque...
Source: Clinical Genetics - September 6, 2023 Category: Genetics & Stem Cells Authors: Mohamed S Abdel-Hamid Ghada M H Abdel-Salam Sherif F Abdel-Ghafar Maha S Zaki Source Type: research
Delineating the phenotype of PNPLA8-related mitochondriopathies
Clin Genet. 2023 Sep 6. doi: 10.1111/cge.14421. Online ahead of print.ABSTRACTPathogenic variants in PNPLA8 have been described either with congenital onset displaying congenital microcephaly, early onset epileptic encephalopathy and early lethality or childhood neurodegeneration with progressive microcephaly. Moreover, a phenotype comprising adulthood onset cerebellar ataxia and peripheral neuropathy was also reported. To our knowledge, only six patients with biallelic variants in PNPLA8 have been reported so far. Here, we report the clinical and molecular characterizations of three additional patients in whom exome seque...
Source: Clinical Genetics - September 6, 2023 Category: Genetics & Stem Cells Authors: Mohamed S Abdel-Hamid Ghada M H Abdel-Salam Sherif F Abdel-Ghafar Maha S Zaki Source Type: research
Delineating the phenotype of PNPLA8-related mitochondriopathies
Clin Genet. 2023 Sep 6. doi: 10.1111/cge.14421. Online ahead of print.ABSTRACTPathogenic variants in PNPLA8 have been described either with congenital onset displaying congenital microcephaly, early onset epileptic encephalopathy and early lethality or childhood neurodegeneration with progressive microcephaly. Moreover, a phenotype comprising adulthood onset cerebellar ataxia and peripheral neuropathy was also reported. To our knowledge, only six patients with biallelic variants in PNPLA8 have been reported so far. Here, we report the clinical and molecular characterizations of three additional patients in whom exome seque...
Source: Clinical Genetics - September 6, 2023 Category: Genetics & Stem Cells Authors: Mohamed S Abdel-Hamid Ghada M H Abdel-Salam Sherif F Abdel-Ghafar Maha S Zaki Source Type: research
