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| Infertility and Recurrent Pregnancy Loss v0.63 | KHDC3L |
Jasmine Chew changed review comment from: Biallelic variants have been reported for several unrelated families with recurrent complete hydatidiform mole (CHM) pregnancy- predominantly biparental and RPL- PMID: 21885028, 19246479, 23232697. New evidence- i) PMID 31847873: homozygous LOF variant in a woman with multiple consanguineous marriages in her extended family and history of 2 biparental complete hydatidiform mole (BiCHM) and methylation study on her oocytes revealed a genome-wide deficit of DNA methylation compared with normal human oocytes. ii) PMID: 31609975- two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and homologous recombination (HR) repair. Also provided functional evidence that KHDC3L dysfunction causes PARP1 inhibition and HR-mediated DNA repair deficiency, which is synthetically lethal. iii) PMID: 29606347- a novel homozygous frameshift p.Q15Rfs*25 variant in a female patient (II-1) from family 4 with a history of 2 spontaneous abortions and x2 partial hydatidiform moles, and her embryos formed after ICSI are fertilized normally but arrest at the morula stage. Sources: Literature; to: Biallelic variants have been reported for several unrelated families with recurrent complete hydatidiform mole (CHM) pregnancy- predominantly biparental and RPL- PMID: 21885028, 19246479, 23232697. New evidence (biallelic variants and CHM pregnancy)- i) PMID 31847873: homozygous LOF variant in a woman with multiple consanguineous marriages in her extended family and history of 2 biparental complete hydatidiform mole (BiCHM) and methylation study on her oocytes revealed a genome-wide deficit of DNA methylation compared with normal human oocytes. ii) PMID: 31609975- two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and homologous recombination (HR) repair. Also provided functional evidence that KHDC3L dysfunction causes PARP1 inhibition and HR-mediated DNA repair deficiency, which is synthetically lethal. iii) PMID: 29606347- a novel homozygous frameshift p.Q15Rfs*25 variant in a female patient (II-1) from family 4 with a history of 2 spontaneous abortions and x2 partial hydatidiform moles, and her embryos formed after ICSI are fertilized normally but arrest at the morula stage. New evidence (monoallelic variants and RPL)- i) PMID: 34925444- a heterozygous in frame deletion in KHDC3L (p.146_156del) in a 31-year-old woman with a history of two miscarriages. ii) PMID: 31609975- heterozygous deletions (p.150_160del and p.150_172del) were found in patients experiencing RPL without forming an hydatidiform mole. Note: All of the deletions in patients with RPL affected the Thr156 residue, a critical phosphorylation site for normal KHDC3L protein function. Loss of Thr156 results in impaired PARP1 activation and HR repair. Sources: Literature |
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| Infertility and Recurrent Pregnancy Loss v0.63 | KHDC3L | Jasmine Chew edited their review of gene: KHDC3L: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.26 | KHDC3L | Zornitza Stark Marked gene: KHDC3L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.26 | KHDC3L | Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.26 | KHDC3L | Zornitza Stark Classified gene: KHDC3L as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.26 | KHDC3L | Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.17 | KHDC3L | Jasmine Chew edited their review of gene: KHDC3L: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infertility and Recurrent Pregnancy Loss v0.12 | KHDC3L |
Jasmine Chew gene: KHDC3L was added gene: KHDC3L was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: KHDC3L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KHDC3L were set to 21885028; 19246479; 23232697; 31847873; 31609975; 29606347 Phenotypes for gene: KHDC3L were set to Recurrent hydatidiform mole 2, MIM# 614293 Added comment: Biallelic variants have been reported for several unrelated families with recurrent complete hydatidiform mole (CHM) pregnancy- predominantly biparental and RPL- PMID: 21885028, 19246479, 23232697. New evidence- i) PMID 31847873: homozygous LOF variant in a woman with multiple consanguineous marriages in her extended family and history of 2 biparental complete hydatidiform mole (BiCHM) and methylation study on her oocytes revealed a genome-wide deficit of DNA methylation compared with normal human oocytes. ii) PMID: 31609975- two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and homologous recombination (HR) repair. Also provided functional evidence that KHDC3L dysfunction causes PARP1 inhibition and HR-mediated DNA repair deficiency, which is synthetically lethal. iii) PMID: 29606347- a novel homozygous frameshift p.Q15Rfs*25 variant in a female patient (II-1) from family 4 with a history of 2 spontaneous abortions and x2 partial hydatidiform moles, and her embryos formed after ICSI are fertilized normally but arrest at the morula stage. Sources: Literature |
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