Novel compound heterozygous mutation in WEE2 is associated with fertilization failure: case report of an infertile woman and literature review

Abstract Background Fertilization failure after intracytoplasmic sperm injection continues to affect couples and the etiology is not well-understood. Case presentation We characterized a couple with 2-year history of primary unexplained infertility. Three different assisted reproduction attempts (IVF + rescue ICSI, ICSI and ICSI-AOA) showed repeated fertilization failure for MII oocyte retrieval after controlled ovarian hyperstimulation. After whole-exome sequencing and sanger sequencing of the couple and their family members, variant pathogenicity was assessed using SIFT, PolyPhen2, Mutation Taster, and Human Splicing Finder software. We identified novel compound heterozygous mutations, c.1535 + 3A > G and c.946C > T (p. Leu316Phe), in WEE2 in the female proband. Trios analysis of the variations revealed an autosomal recessive pattern. c.1535 + 3A > G in WEE2 was predicted to break the wild-type donor site and affect splicing, and the missense mutation c.946C > T (p. Leu316Phe) of WEE2 was predicted to be pathogenic. Conclusion A novel compound heterozygous mutation in WEE2 was identified in an infertile female who experienced repeated fertilization failure even after ICSI-AOA. These novel mutations in WEE2 provided genetic evidence for fertilization failure.

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Whole-exome sequencing identifies a novel compound heterozygous mutation of ANKS6 gene in a Chinese nephronophthisis patient

Clinica Chimica Acta ◽

10.1016/j.cca.2019.10.030 ◽

2020 ◽

Vol 501 ◽

pp. 131-135

Author(s):

Boliang Fang ◽

Jun Guo ◽

Chanjuan Hao ◽

Ruolan Guo ◽

Suyun Qian ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Whole Exome

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Complex medical history of a patient with a compound heterozygous mutation in C1QC

Lupus ◽

10.1177/0961203319865029 ◽

2019 ◽

Vol 28 (10) ◽

pp. 1255-1260 ◽

Cited By ~ 1

Author(s):

R Lubbers ◽

L J J Beaart-van de Voorde ◽

K van Leeuwen ◽

M de Boer ◽

K A Gelderman ◽

...

Keyword(s):

Western Blot ◽

Medical History ◽

Rna Sequencing ◽

Lupus Erythematosus ◽

Compound Heterozygous Mutation ◽

Enzyme Linked Immunosorbent Assay ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Classical Pathway ◽

History Of

Introduction C1q is an essential part of the classical pathway of complement activation. Genetic deficiencies, caused by homozygous mutations in one of the C1q genes, are rare and are strongly associated with development of systemic lupus erythematosus (SLE). Here we describe a C1q-deficient patient with a compound heterozygous mutation. Material and methods Serum was analysed with enzyme-linked immunosorbent assay (ELISA) and Western blot for the presence of C1q, and DNA and RNA sequencing was performed to identify the mutations and confirm that these were located on different chromosomes. Results The medical history of the patient includes SLE diagnosis at age 11 years with cerebral involvement at age 13, various infections, osteonecrosis and hemophagocytic syndrome. Using ELISA and Western blot, we confirmed the absence of C1q in the serum of the patient. Using DNA sequencing, two mutations in the C1QC gene were identified: c.100G > A p.(Gly34Arg) and c.205C > T p.(Arg69X). With RNA sequencing we confirmed that the mutations are located on different chromosomes. Discussion The patient described in this case report has a compound heterozygous mutation in C1QC resulting in C1q deficiency.

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Identification of Novel ADGRV1 and KCNC2 Variants Using Whole-Exome Sequencing in Two Colombian Patients with Usher and Encephalopathy Syndromes

10.21203/rs.3.rs-923411/v1 ◽

2021 ◽

Author(s):

Estephania Candelo ◽

Lorena Diaz-Ordoñez ◽

Rafael Pacheco ◽

Emelina Ruiz ◽

Harry Pachajoa

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Usher Syndrome ◽

Epileptic Encephalopathy ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Epilepsy Syndrome ◽

Compound Heterozygous ◽

Whole Exome ◽

Excellent Method

Abstract Introduction: Usher syndrome has a broad phenotypic and genotypic spectrum. Developmental and epileptic encephalopathy-52 (DEE52) is a sever autosomal recessive seizure disorder that is characterized by infantile onset of refractory seizures, consequently resulting in delayed global development. This study aimed to describe the clinical features and to investigate the four variants identified in a Colombian family with Usher syndrome and KCNC2 encephalopathy syndrome.Methods and Results: We present a case of a family with two clinically relevant phenotypes: a mother with a compound heterozygous mutation causing Usher Syndrome, type IIC (USH2C) and her 15-year-old son who carried one heterozygous variant in the KCNC2 gene (p.P470S) and two cis mutations (p.V2927I and p.Q4955EfsTer10) in the ADGRV1 gene segregated from his mother, and a second non-disrupted allele. Owing to this, the boy did not present with USH2C but presented a developmental epilepsy syndrome. His younger sibling was unaffected, although he did inherit the trans mutation in a single pathogenic allele from his mother.Discussion and Conclusion: Whole-exome sequencing helps detect genes related to known and novel hearing loss and seizure syndrome. However, familiar segregation studies are an excellent method to clarify genotype-phenotype correlation in families, where multiple genes of clinically relevant have been identified. This method helps determine the genotype-phenotype relationship of a disease, which is associated with the clinical presentation and determines the pathogenicity of variants that are classified as variants of uncertain clinical significance.

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Novel Compound Heterozygous Mutation in TRAPPC9 Gene: The Relevance of Whole Genome Sequencing

Genes ◽

10.3390/genes12040557 ◽

2021 ◽

Vol 12 (4) ◽

pp. 557

Author(s):

Maria Isabel Alvarez-Mora ◽

Jordi Corominas ◽

Christian Gilissen ◽

Aurora Sanchez ◽

Irene Madrigal ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Missense Variant ◽

Autism Spectrum ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Whole Genome ◽

Whole Exome ◽

Considerable Impact

Advances in high-throughput technologies and its implementation worldwide have had a considerable impact on the elucidation of the molecular causes underlying neurodevelopmental psychiatric disorders, especially for autism spectrum disorder and intellectual disability (ID). Nevertheless, etiology remains elusive in close to 50% of cases, even in those families with multiple affected individuals, strongly hinting at a genetic cause. Here we present a case report of two siblings affected with severe ID and other comorbidities, who embarked on a genetic testing odyssey until diagnosis was reached by using whole genome sequencing (WGS). WGS identified a maternally inherited novel missense variant (NM_031466.7:c.1037G > A; p.Gly346Glu) and a paternally inherited 90 kb intragenic deletion in TRAPPC9 gene. This report demonstrates the clinical utility of WGS in patients who remain undiagnosed after whole exome sequencing.

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Whole-Exome Sequencing Identified a Novel Compound Heterozygous Mutation of LRRC6 in a Chinese Primary Ciliary Dyskinesia Patient

BioMed Research International ◽

10.1155/2018/1854269 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Lv Liu ◽

Hong Luo

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Primary Ciliary Dyskinesia ◽

Premature Stop Codon ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Mrna Levels ◽

Whole Exome ◽

Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a clinical rare peculiar disorder, mainly featured by respiratory infection, tympanitis, nasosinusitis, and male infertility. Previous study demonstrated it is an autosomal recessive disease and by 2017 almost 40 pathologic genes have been identified. Among them are the leucine-rich repeat- (LRR-) containing 6 (LRRC6) codes for a 463-amino-acid cytoplasmic protein, expressed distinctively in motile cilia cells, including the testis cells and the respiratory epithelial cells. In this study, we applied whole-exome sequencing combined with PCD-known genes filtering to explore the genetic lesion of a PCD patient. A novel compound heterozygous mutation in LRRC6 (c.183T>G/p.N61K; c.179-1G>A) was identified and coseparated in this family. The missense mutation (c.183T>G/p.N61K) may lead to a substitution of asparagine by lysine at position 61 in exon 3 of LRRC6. The splice site mutation (c.179-1G>A) may cause a premature stop codon in exon 4 and decrease the mRNA levels of LRRC6. Both mutations were not present in our 200 local controls, dbSNP, and 1000 genomes. Three bioinformatics programs also predicted that both mutations are deleterious. Our study not only further supported the importance of LRRC6 in PCD, but also expanded the spectrum of LRRC6 mutations and will contribute to the genetic diagnosis and counseling of PCD patients.

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Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios

Frontiers in Genetics ◽

10.3389/fgene.2021.606970 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shin-Yu Lin ◽

Gwo-Tsann Chuang ◽

Chien-Hui Hung ◽

Wei-Chou Lin ◽

Yung-Ming Jeng ◽

...

Keyword(s):

Exome Sequencing ◽

Neonatal Death ◽

Autosomal Recessive ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Early Neonatal Death ◽

Renal Tubular Dysgenesis ◽

Whole Exome ◽

Renal Tubular

Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G > T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.

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A Case Report: Gitelman Syndrome or Bartter Syndrome?

10.21203/rs.3.rs-36606/v1 ◽

2020 ◽

Author(s):

YuanBin WU ◽

Jingjing Hu ◽

Bo Wang ◽

Dongxin Yang ◽

Han Zheng ◽

...

Keyword(s):

Bartter Syndrome ◽

Gitelman Syndrome ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Slc12a3 Gene ◽

Hypokalemic Alkalosis ◽

Chinese Girl ◽

History Of ◽

Laboratory Examinations

Abstract Background: Gitelman syndrome (GS) is a rare autosomal recessive inherited tubular disease which is caused by mutation in the SLC12A3 gene. It is characterized by hypokalemic alkalosis with hypomagnesemia and hypocalciuria, and can cause serious complications such as arrhythmia, syncope, sudden death, etc. Bartter syndrome (BS) is similar to Gitelman syndrome in clinical and laboratory examinations. If lack of sufficient understanding of the disease, it is easy to cause misdiagnosis and missed diagnosis. Case presentation: A 6-year-old Chinese girl presented with history of hand and foot spasms and was diagnosed with hypokalemia. Although multiple symptomatic treatments of potassium supplementation was given, is the concentration of potassium was still at a low level. Gene analysis revealed that the presence of two heterozygous mutations, i.e. a missense mutation c.248G> A and a frameshift mutation c.2875_2876del, in the SLC12A3 gene.The child was diagnosed with Gitelman syndrome(GS) due to SLC12A3 compound heterozygous mutation. Through treatment, the level of ion metabolism in children remains stable. Conclusions: By reviewing its clinical characteristics and diagnosis and treatment ideas, we can help improve clinicians' understanding of children's GS.

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Aicardi-Goutières Syndrome due to a SAMHD1 Mutation Presenting with Deep White Matter Cysts

Molecular Syndromology ◽

10.1159/000518941 ◽

2021 ◽

pp. 1-7

Author(s):

Barbara Oleksy ◽

Hanna Mierzewska ◽

Jolanta Tryfon ◽

Maria Wypchło ◽

Krystyna Wasilewska ◽

...

Keyword(s):

Type I Interferon ◽

Interferon Response ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Type I ◽

Deep White Matter ◽

Temporal Lobes ◽

Whole Exome ◽

Polish Patient

We report on the first Polish patient diagnosed with the Aicardi-Goutières syndrome 5 (AGS5). AGS is caused by mutations in one of 9 genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, IFIH, LSM11, RNU7-1) which stimulate the type I interferon response. The diagnosis was confirmed by identifying a compound heterozygous mutation p.(Phe165Ser)/p.(Gln235*) in the SAMHD1 gene using whole-exome sequencing. The cystic lesions in the temporal lobes are an uncommon finding in the presented patient carrying a SAMHD1 mutation. Reporting new cases expands the range of phenotypes and plays the crucial role in understanding the AGS pathogenesis and creates new therapy approaches.

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Congenital cataract with LSS gene mutations: a new case report

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0101 ◽

2017 ◽

Vol 30 (11) ◽

Cited By ~ 9

Author(s):

Xiaodan Chen ◽

Li Liu

Keyword(s):

Case Report ◽

Exome Sequencing ◽

Pediatric Patient ◽

Congenital Cataract ◽

Gene Mutations ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Case Presentation ◽

Whole Exome

AbstractBackground:Congenital cataract is one of the major causes of blindness and amblyopia in children. About one-third of the cases are inherited.Case presentation:We applied whole exome sequencing for a pediatric patient with congenital cataract, small penis, baldness and absence of eyebrows and detected a compound heterozygous mutation in the lanosterol synthase (Conclusions:We concluded that the mutations affect the structural stability of the protein to some extent.

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