SCNN1B and CA12 play vital roles in occurrence of congenital bilateral absence of vas deferens (CBAVD)

Shen, Ying; Yue, Huanxun; Li, Fuping; Hu, Fengyun; Li, Xiaoliang; Qian, Wensheng; Zhao, Wenrui; Jing, Ji-Gang; Cai, Diming; Jiang, Xiaohui

doi:10.4103/aja.aja_112_18

Cited by 11 publications

(5 citation statements)

References 12 publications

(11 reference statements)

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“…Several of these candidate genes such as ADGRG2 and SLC9A3 have been validated in knockout mice and their physiology explored in this animal model (Davies et al 2004 ; Wang et al 2017 ). Recently, an integrative multi-omic approach that combines WGS, whole DNA methylome analysis, and RNA sequencing has led to the identification of two new candidate genes, SCNN1B and CA12, in an individual with iCBAVD (Shen et al 2019 ). However, despite these advances, there is still no genetic diagnosis for at least a quarter of the CAVDs, most of which are CUAVDs.…”

Section: Genetics Of Cavdmentioning

confidence: 99%

Genetics of the congenital absence of the vas deferens

2020

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Congenital absence of the vas deferens (CAVD) may have various clinical presentations depending on whether it is bilateral (CBAVD) or unilateral (CUAVD), complete or partial, and associated or not with other abnormalities of the male urogenital tract. CBAVD is usually discovered in adult men either during the systematic assessment of cystic fibrosis or other CFTR-related conditions, or during the exploration of isolated infertility with obstructive azoospermia. The prevalence of CAVDs in men is reported to be approximately 0.1%. However, this figure is probably underestimated, because unilateral forms of CAVD in asymptomatic fertile men are not usually diagnosed. The diagnosis of CAVDs is based on clinical, ultrasound, and sperm examinations. The majority of subjects with CAVD carry at least one cystic fibrosis-causing mutation that warrants CFTR testing and in case of a positive result, genetic counseling prior to conception. Approximately 2% of the cases of CAVD are hemizygous for a loss-of-function mutation in the ADGRG2 gene that may cause a familial form of X-linked infertility. However, despite this recent finding, 10-20% of CBAVDs and 60-70% of CUAVDs remain without a genetic diagnosis. An important proportion of these unexplained CAVDs coexist with a solitary kidney suggesting an early organogenesis disorder (Wolffian duct), unlike CAVDs related to CFTR or ADGRG2 mutations, which might be the result of progressive degeneration that begins later in fetal life and probably continues after birth. How the dysfunction of CFTR, ADGRG2, or other genes such as SLC29A3 leads to this involution is the subject of various pathophysiological hypotheses that are discussed in this review.

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Section: Genetics Of Cavdmentioning

confidence: 99%

Genetics of the congenital absence of the vas deferens

2020

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“…38 Other genetic associations with CAVD are mutations in ADGRG2, SLC9A3, SCNN1B, CA12 and copynumber variations in PANK2 genes. [39][40][41][42] It is often found that men with CBAVD have normal production of spermatozoa, but due to agenesis of the vas deferens, there are no sperms in the ejaculate. This suggests that men with CBAVD can attain fatherhood by using ART.…”

Section: Male Infertilitymentioning

confidence: 99%

The Genetic and Genomic Landscape of Human Reproductive Disorders: An Overview with Our Experience

Halder

Sharma²,

Rana³

et al. 2023

MRAJ

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Genetics and genomics play a role in the causation of various human diseases. A large number of human reproductive disorders also arise as a result of genetic and genomic abnormalities. Reproductive disorders associated with predominantly genetics and genomic abnormalities are infertility, early pregnancy loss, congenital malformations, difference or disorder of sex development and reproductive cancers. The genetic etiology of human reproductive disorders is increasing with improved molecular biology techniques such as DNA microarray and next-generation sequencing. Infertility is one of the significant areas of reproductive disorders where genetics/genomics plays a substantial role and may result from chromosomal, copy number variation, Yq & pseudo autosomal region microdeletion/microduplication, gene mutation (monogenic, oligogenic, polygenic), multifactorial, epigenetic, mitochondrial, etc. abnormalities. All idiopathic infertile couples should be screened for genetic disorders before assisted reproduction to prevent transmission, if any, in offspring. Pregnancy wastage in early pregnancy is very high (about 70%) and is mainly related to chromosome number, copy number variation, and some monogenic or epigenetic abnormalities. Therefore, all early pregnancy loss cases should also be tested for genetic causes. Congenital malformations are structural defects in embryo, fetus, or newborns and affect about 3% (major malformations) of all births. The malformations could be due to the abnormalities of chromosomes, copy number variation, monogenic, oligogenic, multifactorial, or environmental. Array CGH &/or NGS should be used as the first step to screen congenital malformations. Differences/disorder of sex development is a developmental defect in which the determination and/or differentiation of chromosomal, gonadal, or phenotypic/anatomic sex is abnormal. It is a common disorder and is primarily related to genetic abnormalities. Therefore, a precise diagnosis, mainly through an array CGH and/or NGS, is crucial for the proper management to prevent future psychosexual problems and another birth with the disorder. Cancer is a genomic disorder characterized by genomic instability (due to a defect in DNA repair mechanism), uncontrolled replication (due to lack of response to inhibitory factors/loss of contact inhibition), neo-angiogenesis, invasion and metastasis. All cancer cases should be investigated for genomic markers (both hereditary and somatic) for precise diagnosis, prognosis, and genetic counseling. In this review, we will try to evaluate the role of genetics and genomics in the above-mentioned reproductive disorders, along with genetic & genomic techniques used and reproductive counseling in addition to our experiences.

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“…[ 67 68 ] PANK2 , SCNN1B , and CA12 are also reported in CBAVD. [ 69 70 ] These shreds of evidence suggest the need for expanding diagnostics of CAVD in addition to CFTR .…”

Section: G Enetics Of O Bstructive a Zoospermia D Ue To V mentioning

confidence: 99%

Genetics of male infertility – Present and future: A narrative review

2021

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Infertility affects 8%–12% of couples worldwide with a male factor contributing to nearly 50% of couples either as a primary or contributing cause. Several genetic factors that include single-gene and multiple-gene defects associated with male infertility were reported in the past two decades. However, the etiology remains ambiguous in a majority of infertile men (~40%). The objective of this narrative review is to provide an update on the genetic factors associated with idiopathic male infertility and male reproductive system abnormalities identified in the last two decades. We performed a thorough literature search in online databases from January 2000 to July 2021. We observed a total of 13 genes associated with nonobstructive azoospermia due to maturation/meiotic arrest. Several studies that reported novel genes associated with multiple morphological abnormalities of the sperm flagella are also discussed in this review. ADGRG2 , PANK2 , SCNN1B , and CA12 genes are observed in non- CFTR- related vas aplasia. The genomic analysis should be quickly implemented in clinical practice as the detection of gene abnormalities in different male infertility phenotypes will facilitate genetic counseling.

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SCNN1B and CA12 play vital roles in occurrence of congenital bilateral absence of vas deferens (CBAVD)

Cited by 11 publications

References 12 publications

Genetics of the congenital absence of the vas deferens

Genetics of the congenital absence of the vas deferens

The Genetic and Genomic Landscape of Human Reproductive Disorders: An Overview with Our Experience

Genetics of male infertility – Present and future: A narrative review

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