Symptoms related to a genetic cause
Infertility is a complex disease of the reproductive system characterized by the inability to achieve pregnancy after more than 12 months of regular, unprotected sexual intercourse. It has been estimated that as many as 15% of all couples wishing to conceive are affected by infertility1,2; it is generally attributed to males and females equally. Indications of infertility in women include irregular or missed periods, polycystic ovarian syndrome or endometriosis; in men infertility is typically suggested by low (or no) sperm count or low sperm motility.
Genetic testing can be the key for a significant number of infertile couples trying to have children. Understanding the reason for infertility can often lead to success with a range of assisted reproductive techniques. Counseling of parents can explain any potential to transmit genetic abnormalities that may affect the health of their offspring.
- Individuals with presentation of the most common symptoms of infertility such as amenorrhea, azoospermia, secondary sex character findings
- Individuals with a positive family history of infertility
- Individuals without a positive family history but with characteristic symptoms
- Individuals with a negative but suspected family history in order to perform proper genetic counseling (prenatal analyses are recommended in families of affected individuals)
Confirmation of a clinical diagnosis through genetic testing allows for genetic counseling and may lead to immediate medical management. For each presented case and phenotype, a full medical report will be produced including a tailored diagnostic strategy.
Clinical symptoms are not always the product of the same gene or genetic variation; any diagnosis is determined as a combination of the in-depth clinical information provided and the identified genetic cause.
What do we know about reproductive system diseases?
Reproductive genetics involves a wide array of genetic tests that are conducted with the intent of informing individuals about the possible outcomes of current or future pregnancies. Infertility can be the result of genetic and non-genetic factors, and it is often multifactorial, polygenic or a combination of both. However, specific genes and mutations have been confirmed to be associated with infertility phenotypes in males, females or both, and our knowledge of the nature of the basis of infertility is continually growing.
Roughly 10% of infertility cases have a genetic etiology. Known genetic causes of infertility include chromosomal aberrations, single gene variants and phenotypes with multifactorial inheritance3.
A recent survey of published literature reported over 350 genes reported that play a role in human infertility and/or reproduction4, with ~15% locating to either sex chromosome (X and Y). These genes represent a wide range of functions including sex hormone, organ development, growth and germ cell production.
Testing for reproductive system
Single Gene Analysis
46,XX sex reversal type 1
46,XY sex reversal type 8, modifier of
Azoospermia induced by Y chromosome microdeletions
Congenital bilateral absence of vas deferens
Deafness and male infertility
Deafness and male infertility, CATSPER2 related
Disorders of sex development with cleft palate
Follicle-stimulating hormone deficiency, isolated
Hydatidiform mole, recurrent, type 2
Hypogonadotropic hypogonadism type 6 with or without anosmia
Hypogonadtropic hypogonadism type 14
Hypospadias type 1, X-linked
Hypospadias type 2, X-linked
Leydig cell hypoplasia type 1
Oocyte maturation defect
Ovarian dysgenesis type 1
Ovarian dysgenesis type 2
Persistent Mullerian duct syndrome type 1
Persistent Mullerian duct syndrome type 2
Preeclampsia/eclampsia type 5
Pregnancy loss, recurrent, C4BPA related
Pseudohermaphroditism with gynecomastia
Testicular anomalies with or without congenital heart disease
What can CENTOGENE do for you and your patients?
CENTOGENE is a global leader in the diagnosis of rare genetic diseases and has received multiple international accreditations (ISO/EN 15189, CAP and CLIA) that confirm the highest standards for diagnostic testing and reporting. Our experience, combined with our scientific expertise and medical competence, has allowed the application of state-of-the-art science and technology and the development of a proprietary mutation database.
CENTOGENE has identified genetic variants associated with reproductive genetics in more than 35 different genes.
CentoMD® is the world’s largest mutation database for rare diseases, 58% of which is made up of unpublished variants. We carefully curate and document all variants that have clinical relevance for related symptoms, allowing the most comprehensive diagnosis of a reproductive disease.
- World Health Organization. Report of the Meeting on the Prevention of Infertility at the Primary Health Care Level. WHO, Geneva; 1983. WHO/MCH/1984.4.
- Boivin J, Bunting L, Collins JA, & Nygren KG (2007). International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Human reproduction, 22(6), 1506-1512.
- Shah K, Sivapalan G, Gibbons N, Tempest H, & Griffin DK (2003). The genetic basis of infertility. Reproduction, 126(1), 13-25.
- Butler MG, Rafi SK, McGuire A, & Manzardo AM (2016). Currently recognized clinically relevant and known genes for human reproduction and related infertility with representation on high-resolution chromosome ideograms. Gene, 575(1), 149-159.
Scientific Articles for Reproductive
Carrier screening is a genetic test used to determine if a healthy person is a carrier of a recessive genetic disease. The goal of carrier screening is to help individuals understand their risks of having a child with a genetic disorder and review the range of options available to guide pregnancy…
Proof-of-principle rapid noninvasive prenatal diagnosis of autosomal recessive founder mutations. Ten parental alleles in eight unrelated fetuses were diagnosed successfully based on the noninvasive method developed in this study.
Validation of a Semiconductor Next-Generation Sequencing Assay for the Clinical Genetic Screening of CFTR
Genetic testing for cystic fibrosis and CFTR-related disorders mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the CFTR gene. We have explored a more efficient genetic screening strategy based on next-generation sequencing of the CFTR gene.