Human oocyte maturation arrest caused by a novel missense mutation in TUBB8

Objective To explore the etiology of human oocyte maturation arrest in two infertile Chinese sisters. Methods Clinical examination and genetic testing of all available family members were conducted, and the findings were used to create a pedigree. Mutation screening using PCR amplification and DNA Sanger sequencing of the entire tubulin beta 8 class VIII gene ( TUBB8) including intron–exon boundaries was performed to identify mutations. Results A novel missense TUBB8 mutation (c.1054G > T, p.A352S) in the patient and her elder sister was detected and shown to be associated with oocyte maturation arrest. Conclusion Our findings expand the known mutation spectrum of TUBB8 and provide insights into the etiology of human oocyte maturation arrest.

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PRPF3-Associated Autosomal Dominant Retinitis Pigmentosa and CYP4V2-Associated Bietti’s Crystalline Corneoretinal Dystrophy Coexist in a Multigenerational Chinese Family

Journal of Ophthalmology ◽

10.1155/2017/4156386 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10

Author(s):

Xiaohong Meng ◽

Qiyou Li ◽

Hong Guo ◽

Haiwei Xu ◽

Shiying Li ◽

...

Keyword(s):

Missense Mutation ◽

Clinical Features ◽

Sanger Sequencing ◽

Mutation Screening ◽

Retinal Dystrophy ◽

Family Members ◽

Large Family ◽

Chinese Family ◽

Compound Heterozygous ◽

Genetic Characteristics

Purpose. To characterize the clinical and molecular genetic characteristics of a large, multigenerational Chinese family showing different phenotypes. Methods. A pedigree consisted of 56 individuals in 5 generations was recruited. Comprehensive ophthalmic examinations were performed in 16 family members affected. Mutation screening of CYP4V2 was performed by Sanger sequencing. Next-generation sequencing (NGS) was performed to capture and sequence all exons of 47 known retinal dystrophy-associated genes in two affected family members who had no mutations in CYP4V2. The detected variants in NGS were validated by Sanger sequencing in the family members. Results. Two compound heterozygous CYP4V2 mutations (c.802-8_810del17insGC and c.992A>C) were detected in the proband who presented typical clinical features of BCD. One missense mutation (c.1482C>T, p.T494M) in the PRPF3 gene was detected in 9 out of 22 affected family members who manifested classical clinical features of RP. Conclusions. Our results showed that two compound heterozygous CYP4V2 mutations caused BCD, and one missense mutation in PRPF3 was responsible for adRP in this large family. This study suggests that accurate phenotypic diagnosis, molecular diagnosis, and genetic counseling are necessary for patients with hereditary retinal degeneration in some large mutigenerational family.

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A homozygous missense mutation in TBPL2 is associated with oocyte maturation arrest and degeneration

Clinical Genetics ◽

10.1111/cge.13993 ◽

2021 ◽

Author(s):

Yu Wang ◽

Mingfei Xiang ◽

Zhaojuan Yu ◽

Yan Hao ◽

Qianhua Xu ◽

...

Keyword(s):

Missense Mutation ◽

Oocyte Maturation ◽

Maturation Arrest ◽

Homozygous Missense Mutation

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PROOF OF CONCEPT OF A TREATMENT FOR HUMAN OOCYTE MATURATION ARREST;TRANSVAGINAL OVARIAN NEEDLE INJURY PRECEEDING LETROZOLE PRIMING IN VITRO MATURATION

Fertility and Sterility ◽

10.1016/j.fertnstert.2020.09.107 ◽

2020 ◽

Vol 114 (3) ◽

pp. e558-e559

Author(s):

Safak Hatirnaz ◽

Ebru Hatirnaz ◽

Alper Basbug ◽

Michael H. Dahan ◽

Kaan Hatirnaz

Keyword(s):

Oocyte Maturation ◽

In Vitro Maturation ◽

Human Oocyte ◽

Proof Of Concept ◽

Maturation Arrest

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Identification of Novel Mutations in CDC20: Expanding the Mutational Spectrum for Female Infertility

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.647130 ◽

2021 ◽

Vol 9 ◽

Author(s):

Lin Zhao ◽

Yichun Guan ◽

Qingxia Meng ◽

Weijie Wang ◽

Ling Wu ◽

...

Keyword(s):

Embryonic Development ◽

Oocyte Maturation ◽

Female Infertility ◽

Early Embryonic Development ◽

Human Reproduction ◽

Human Oocyte ◽

Fertilization Failure ◽

Novel Mutations ◽

Maturation Arrest ◽

Biallelic Mutations

Oocyte maturation and fertilization are fundamental processes for successful human reproduction, and abnormalities in these processes will cause infertility. Recently, we identified biallelic mutations in CDC20 that are responsible for human oocyte maturation arrest, fertilization failure, and early embryonic development arrest. In this study, we screened for further CDC20 mutations in a new cohort of patients with abnormalities in oocyte maturation, fertilization, and early embryonic development. Through whole-exome sequencing, we identified the four novel mutations c.887G > A (p. Arg296Gln), c.964C > T (p.Arg322∗), c.1155G > C (p.Trp385Cys), and c.330 + 1G > A (p. Glu111Ilefs∗36) and one previously reported mutation c.965G > A (p.Arg322Gln) in CDC20 in four infertile individuals from three independent families. The patients had different phenotypes of oocyte maturation arrest and fertilization failure resulting from the different mutations. This study confirms our previous research and expands the spectrum of known mutations in CDC20, providing new evidence supporting the function of CDC20 in the genetic etiology of female infertility characterized by oocyte maturation arrest and fertilization failure.

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Abnormal neurodevelopment outcome in case of neonatal hyperekplexia secondary to missense mutation in GLRB gene

BMJ Case Reports ◽

10.1136/bcr-2020-236152 ◽

2020 ◽

Vol 13 (12) ◽

pp. e236152

Author(s):

Naveen Parkash Gupta ◽

Vinita Verma ◽

Saurabh Chopra ◽

Vivek Choudhury

Keyword(s):

Genetic Testing ◽

Missense Mutation ◽

Genetic Predisposition ◽

Seizure Disorder ◽

Β Subunit ◽

Tonic Spasm ◽

Initial Improvement ◽

External Stimuli ◽

Neurodevelopment Outcome

Hyperekplexia is an exaggerated startle to external stimuli associated with a generalised increase in tone seen in neonates with both sporadic and genetic predisposition. This is an uncommon neurological entity that is misdiagnosed as seizure. A 28-days-old infant was admitted to us with characteristic intermittent generalised tonic spasm being treated as a seizure disorder. The infant had characteristic stiffening episode, exaggerated startle and non-habituation on tapping the nose. Hyperekplexia was suspected and confirmed by genetic testing (mutation in the β subunit of glycine was found). Initial improvement was seen with the use of clonazepam, which was not sustained. At the age of 4.5 years, the child is still having neurobehavioural issues like hyperactivity and sensory hyper-responsiveness. Usually, hyperekplexia is benign in nature. We report a case of hyperekplexia with non-sense mutation in the β subunit of GlyR gene having abnormal neurodevelopmental findings at 4.5 years.

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Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the early C. elegans embryo

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab063 ◽

2021 ◽

Author(s):

Dorothy Benton ◽

Eva C Jaeger ◽

Arielle Kilner ◽

Ashley Kimble ◽

Josh Lowry ◽

...

Keyword(s):

Missense Mutation ◽

Oocyte Maturation ◽

Protective Role ◽

C Elegans ◽

Direct Target ◽

The One ◽

Actomyosin Cytoskeleton ◽

Embryonic Viability ◽

Anterior Posterior

Abstract Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior-posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. While the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome-cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. While depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development.

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