Mutations of <i><scp>SGO2</scp></i> and <i><scp>CLDN14</scp></i> collectively cause coincidental Perrault syndrome

Faridi, Rabia; Rehman, Atteeq U.; Morell, Robert J.; Friedman, Penelope L.; Demain, Leigh A.M.; Zahra, Sana; Khan, Azhar Ali; Tohlob, Dalia; Assir, Muhammad Zaman Khan; Beaman, Glenda M.; Khan, Shaheen N.; Newman, William G.; Riazuddin, Saima; Friedman, Thomas B.

doi:10.1111/cge.12867

Cited by 47 publications

(28 citation statements)

References 22 publications

(29 reference statements)

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“…A combination of two homozygous mutations leading to a coincidental PS, one in CLDN14 involved in deafness and the other in shugoshin-like 2a (SGO2) encoding shugoshin2, likely involved in POI, have been described [69]. During meiosis in the mouse, SGO2 maintains the integrity of the cohesion complex that tethers sister chromatids.…”

Section: Crossovermentioning

confidence: 99%

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Huhtaniemi

Hovatta

Marca

et al. 2018

Trends in Endocrinology & Metabolism

135

134

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Primary ovarian insufficiency (POI) affects ∼1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of >60 genes emphasize high genetic heterogeneity. Genome-wide association studies have revealed a shared genetic background between POI and reproductive aging. NGS will provide a genetic diagnosis leading to genetic/therapeutic counseling: first, defects in meiosis or DNA repair genes may predispose to tumors; and second, specific gene defects may predict the risk of rapid loss of a persistent ovarian reserve, an important determinant in fertility preservation. Indeed, a recent innovative treatment of POI by in vitro activation of dormant follicles proved to be successful.

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Section: Crossovermentioning

confidence: 99%

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Huhtaniemi

Hovatta

Marca

et al. 2018

Trends in Endocrinology & Metabolism

135

134

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“…In mouse, Sgol2a (encoding shugoshin‐like 2a) is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. In support of the pathogenic role of the SGO2 defect, mutations in other cohesion complex genes also cause infertility . Considering that the proband manifests 2 genetically distinct disorders, deafness and POI, it does not represent true DI, even though they are the hallmark of the PS.…”

Section: Bilineal Inheritance Of 1 Disease or Co‐inheritance Of 2 Difmentioning

confidence: 99%

“…In support of the pathogenic role of the SGO2 defect, mutations in other cohesion complex genes also cause infertility. 40 Considering that the proband manifests 2 genetically distinct disorders, deafness and POI, it does not represent true DI, even though they are the hallmark of the PS.…”

Section: Not Many Dominant Disorders Have This High Frequency It Ismentioning

confidence: 99%

Digenic inheritance and genetic modifiers

Deltas

2018

Clinical Genetics

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Digenic inheritance (DI) concerns pathologies with the simplest form of multigenic etiology, implicating more than 1 gene (and perhaps the environment). True DI is when biallelic or even triallelic mutations in 2 distinct genes, in cis or in trans, are necessary and sufficient to cause pathology with a defined diagnosis. In true DI, a heterozygous mutation in each of 2 genes alone is not associated with a recognizable phenotype. Well-documented diseases with true DI are so far rare and follow non-Mendelian inheritance. DI is also encountered when by serendipity, pathogenic mutations responsible for 2 distinct disease entities are co-inherited, leading to a mixed phenotype. Also, we can consider many true monogenic Mendelian conditions, which show impressively broad spectrum of phenotypes due to pseudo-DI, as a result of co-inheriting genetic modifiers (GMs). I am herewith reviewing examples of GM and embark on presenting some recent notable examples of true DI, with wider discussion of the literature. Undeniably, the advent of high throughput sequencing is bound to unravel more patients suffering with true DI conditions and elucidate many important GM, thus impacting precision medicine.

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“…STAG3 causes non-syndromic POI, while pathogenic variants in SGO2 cause Perrault's syndrome (hearing loss and gonadal dysgenesis). 77,82 Homologous recombination between the paired chromosomes during meiosis requires the synaptonemal complex formation. Recently, the disruption in the function of the protein synaptonemal complex central element protein 1 (SYCE1) has been shown to cause POI in humans.…”

Section: Genetics Of Primary Ovarian Insufficiencymentioning

confidence: 99%

Genetics of Reproductive Aging from Gonadal Dysgenesis through Menopause

Desai

Rajkovic

2017

Semin Reprod Med

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Reproduction is essential for the survival of the species and is influenced by external factors such as smoking and exposure to chemotherapy as well as chronic disorders such as obesity and autoimmunity. Reproductive senescence, such as menopause, is also dependent on multiple intrinsic genetic factors. Reproductive aging is not isolated from an overall aging process, and several studies strongly support the link between the early age of menopause and mortality. The extreme form of reproductive aging is primary ovarian insufficiency (POI) with prevalence ranging from 1 to 5% of the female population. POI has been shown to have long-term consequences on overall health. POI and age of menopause have a significant hereditary component. The population-based genome-wide association studies have identified 44 genomic loci to associate with age of menopause, and 29 of 44 loci harbor DNA damage response genes. Recent application of whole exome sequencing on carefully selected families with POI has also revealed a significant contribution of DNA damage response genes. The inability to repair the DNA damage in both somatic and germ cells might be a predisposing factor for the link between reproductive and overall aging in a subset of individuals with POI. The aim of this review is to characterize recent advances in the genetics of POI and its link with overall health.

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Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome

Cited by 47 publications

References 22 publications

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Digenic inheritance and genetic modifiers

Genetics of Reproductive Aging from Gonadal Dysgenesis through Menopause

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