Comprehensive genetic testing for female and male infertility using next-generation sequencing

Patel, Bonny; Parets, Sasha; Akana, Matthew; Kellogg, Gregory; Jansen, Michael; Chang, Chih-Yu; Cai, Ying; Fox, Rebecca; Niknazar, Mohammad; Shraga, R.; Hunter, Colby; Pollock, Andrew; Wisotzkey, Robert G.; Jaremko, Malgorzata; Bisignano, Alex; Puig, Óscar

doi:10.1007/s10815-018-1204-7

Cited by 61 publications

(33 citation statements)

References 32 publications

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“…However, in light of the recent developments of novel sequencing technologies, it is now possible to consolidate one or multiple tests in a single NGS assay which will help to cut the costs. The first examples of NGS-based screening methods have been described for male infertility (Oud et al 2017; Fakhro et al 2018; Patel et al 2018). The European Society of Human Genetics (ESHG) and the European Society for Human Reproduction and Embryology (ESHRE) have recently made a recommendation for developing and introducing new tests, specifically for extended carrier screening (Harper et al 2018).…”

Section: Discussionmentioning

confidence: 99%

A systematic review and standardized clinical validity assessment of male infertility genes

Oud¹,

Voložonoka

Smits

et al. 2018

Preprint

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Study question Which genes are confidently linked to human male infertility? Summary answer Our systematic literature search and clinical validity assessment reveals that a total of 67 genes are currently confidently linked to 81 human male infertility phenotypes. What is known already The discovery of novel male infertility genes is rapidly accelerating with the availability of Next-Generation Sequencing methods, but the quality of evidence for gene-disease relationships varies greatly. In order to improve genetic research, diagnostics and counseling, there is a need for an evidence-based overview of the currently known genes. Study design, size, duration We performed a systematic literature search and evidence assessment for all publications in Pubmed until June 2018 covering genetic causes of male infertility and/or defective male genitourinary development. Participants/materials, setting, methods Two independent reviewers conducted the literature search and included papers on the monogenic causes of human male infertility and excluded papers on genetic association or risk factors, karyotype anomalies and/or copy number variations affecting multiple genes. Next, the quality and the extent of all evidence supporting selected genes was weighed by a standardized scoring method and used to determine the clinical validity of each gene-disease relationship as expressed by the following six categories: no evidence, limited, moderate, strong, definitive or unable to classify. Main results and the role of chance From a total of 23,031 records, we included 1,286 publications about monogenic causes of male infertility leading to a list of 471 gene-disease relationships. The clinical validity of these gene-disease relationships varied widely and ranged from definitive (n=36) to strong (n=12), moderate (n=33), limited (n=86) or no evidence (n=154). A total of 150 gene-disease relationships could not be classified. Limitations, reasons for caution Our literature search was limited to Pubmed. Wider implications of the findings The comprehensive overview will aid researchers and clinicians in the field to establish gene lists for diagnostic screening using validated gene-disease criteria and identify gaps in our knowledge of male infertility. For future studies, the authors discuss the relevant and important international guidelines regarding research related to gene discovery and provide specific recommendations to the field of male infertility. Study funding/competing interest(s) This work was supported by a VICI grant from The Netherlands Organisation for Scientific Research (918-15-667 to JAV).

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Section: Discussionmentioning

confidence: 99%

A systematic review and standardized clinical validity assessment of male infertility genes

Oud¹,

Voložonoka

Smits

et al. 2018

Preprint

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“…Numerous studies have investigated the genetic link between CFTR mutations and the risk of CBAVD (27)(28)(29)(30). A large number of CFTR mutant alleles have been found in patients with CBAVD.…”

Section: The Cftr Gene In Patients With Cbavdmentioning

confidence: 99%

“…To date, >2,000 CF-causing CFTR mutations have been identified (Table II; genet.sickkids.on.ca/StatisticsPage.html). CFTR gene mutations are divided into six classes, according to the extent of CFTR protein downregulation (28)(29)(30). class i mutations refer to the production of non-functional protein or non-functional mrna products that are degraded by nonsense-mediated mRNA decay (31).…”

Section: The Cftr Gene In Patients With Cbavdmentioning

confidence: 99%

Mutations of the cystic fibrosis transmembrane conductance regulator gene in males with congenital bilateral absence of the vas deferens: Reproductive implications and genetic counseling (Review)

Cui¹,

Wu²,

Li³

et al. 2020

Mol Med Rep

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congenital bilateral absence of the vas deferens (cBaVd) is predominantly caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. cBaVd accounts for 2-6% of male infertility cases and up to 25% of cases of obstructive azoospermia. With the use of pre-implantation genetic diagnosis, testicular or epididymal sperm aspiration, intracytoplasmic sperm injection and in vitro fertilization, patients affected by cBaVd are able to have children who do not carry CFTR gene mutations, thereby preventing disease. Therefore, genetic counseling should be provided to couples receiving assisted reproductive techniques to discuss the impact of CFTR gene mutations on reproductive health. In the present article, the current literature concerning the CFTR gene and its association with CBAVD is reviewed. Contents 1. Introduction 2. Overview of CFTR structure and function 3. The CFTR gene and development of the vas deferens 4. The CFTR gene in patients with CBAVD 5. Hotspot mutation types in patients with CBAVD 6. Assisted reproductive techniques and genetic counselling 7. Conclusions

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“…A custom Phosphorus Affymetrix axiom array (22) was used to confirm all the reportable variants including SNVs, insertions/deletions <15 bp (indels) and CNVs. Microarrays were processed following the manufacturer's instructions.…”

Section: Orthogonal Confirmationmentioning

confidence: 99%

Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

Kellogg¹,

Þórsson

Cai³

et al. 2018

Preprint

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Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality.In the present manuscript, we developed a comprehensive next generation sequencing (NGS) panel which we applied on two different resources of FH in the Icelandic population: 62 subjects from 23 FH families with known or unknown culprit mutations, and a population-based sampling of 315 subjects selected for total cholesterol levels above the 95 th percentile cut-point. The application of the NGS panel revealed significant diagnostic yields in identifying pathogenic LDLR mutations in both family and populationbased genetic testing.

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Comprehensive genetic testing for female and male infertility using next-generation sequencing

Cited by 61 publications

References 32 publications

A systematic review and standardized clinical validity assessment of male infertility genes

A systematic review and standardized clinical validity assessment of male infertility genes

Mutations of the cystic fibrosis transmembrane conductance regulator gene in males with congenital bilateral absence of the vas deferens: Reproductive implications and genetic counseling (Review)

Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

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