Translational aspects of novel findings in genetics of male infertility-status quo 2021.
Br Med Bull
; 140(1): 5-22, 2021 12 16.
Article
in En
| MEDLINE
| ID: mdl-34755838
ABSTRACT
INTRODUCTION:
Male factor infertility concerns 7-10% of men and among these 40-60% remain unexplained. SOURCES OF DATA This review is based on recent published literature regarding the genetic causes of male infertility. AREAS OF AGREEMENT Screening for karyotype abnormalities, biallelic pathogenic variants in the CFTR gene and Y-chromosomal microdeletions have been routine in andrology practice for >20 years, explaining ~10% of infertility cases. Rare specific conditions, such as congenital hypogonadotropic hypogonadism, disorders of sex development and defects of sperm morphology and motility, are caused by pathogenic variants in recurrently affected genes, which facilitate high diagnostic yield (40-60%) of targeted gene panel-based testing. AREAS OF CONTROVERSY Progress in mapping monogenic causes of quantitative spermatogenic failure, the major form of male infertility, has been slower. No 'recurrently' mutated key gene has been identified and worldwide, a few hundred patients in total have been assigned a possible monogenic cause. GROWING POINTS Given the high genetic heterogeneity, an optimal approach to screen for heterogenous genetic causes of spermatogenic failure is sequencing exomes or in perspective, genomes. Clinical guidelines developed by multidisciplinary experts are needed for smooth integration of expanded molecular diagnostics in the routine management of infertile men. AREAS TIMELY FOR DEVELOPING RESEARCH Di-/oligogenic causes, structural and common variants implicated in multifactorial inheritance may explain the 'hidden' genetic factors. It is also critical to understand how the recently identified diverse genetic factors of infertility link to general male health concerns across lifespan and how the clinical assessment could benefit from this knowledge.Key words
Klinefelter syndrome; Y-chromosomal microdeletion; andro-exome pipeline; assisted reproductive technology (ART); azoospermia; chronic disease; clinical guidelines; congenital absence of vas deference; congenital hypogonadotropic hypogonadism; diagnostic gene panel; disorders of sex development; exomes; genetic cause; genetic counselling; genetics; globozoospermia; male infertility; molecular diagnostics; multiple morphological abnormalities of the sperm flagella; oligogenic inheritance; pathogenic variant; pleiotropic genes; severe oligozoospermia; spermatogenic failure; testicular sperm extraction (TESE); translational research
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sex Chromosome Disorders of Sex Development
/
Infertility, Male
Type of study:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Br Med Bull
Year:
2021
Document type:
Article
Affiliation country:
Estonia