Transcription factor SOHLH1 potentially associated with primary ovarian insufficiency

Zhao, Shidou; Li, Guangyu; Dalgleish, Raymond; Vujović, Svetlana; Simpson, Joe Leigh; Qin, Yingying; Ivanisevic, Maja; Ivović, Miomira; Tancic, M.; Al‐Azzawi, Farook; Chen, Zi‐Jiang

doi:10.1016/j.fertnstert.2014.11.011

Cited by 31 publications

(21 citation statements)

References 47 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sohlh1/2 -deficient mice exhibit atrophied ovaries devoid of follicles due to defective primordial-to-primary follicle transition ( Pangas et al , 2006 ; Choi et al , 2008 ). Novel distinct heterozygous variants were identified in both SOHLH1 and SOHLH2 in large cohorts of women with POI of Han Chinese and Serbian origin ( Qin et al , 2014a ; Zhao et al , 2015 ). Plausible pathogenesis might involve disturbing the expression, transactivation or homo-/hetero-dimerization of SOHLH1 or SOHLH2 proteins.…”

Section: Resultsmentioning

confidence: 99%

Genetics of primary ovarian insufficiency: new developments and opportunities

Qin

Jin

Simpson

et al. 2015

Hum. Reprod. Update

Self Cite

416

353

View full text Add to dashboard Cite

BACKGROUNDPrimary ovarian insufficiency (POI) is characterized by marked heterogeneity, but with a significant genetic contribution. Identifying exact causative genes has been challenging, with many discoveries not replicated. It is timely to take stock of the field, outlining the progress made, framing the controversies and anticipating future directions in elucidating the genetics of POI.METHODSA search for original articles published up to May 2015 was performed using PubMed and Google Scholar, identifying studies on the genetic etiology of POI. Studies were included if chromosomal analysis, candidate gene screening and a genome-wide study were conducted. Articles identified were restricted to English language full-text papers.RESULTSChromosomal abnormalities have long been recognized as a frequent cause of POI, with a currently estimated prevalence of 10–13%. Using the traditional karyotype methodology, monosomy X, mosaicism, X chromosome deletions and rearrangements, X-autosome translocations, and isochromosomes have been detected. Based on candidate gene studies, single gene perturbations unequivocally having a deleterious effect in at least one population include Bone morphogenetic protein 15 (BMP15), Progesterone receptor membrane component 1 (PGRMC1), and Fragile X mental retardation 1 (FMR1) premutation on the X chromosome; Growth differentiation factor 9 (GDF9), Folliculogenesis specific bHLH transcription factor (FIGLA), Newborn ovary homeobox gene (NOBOX), Nuclear receptor subfamily 5, group A, member 1 (NR5A1) and Nanos homolog 3 (NANOS3) seem likely as well, but mostly being found in no more than 1–2% of a single population studied. Whole genome approaches have utilized genome-wide association studies (GWAS) to reveal loci not predicted on the basis of a candidate gene, but it remains difficult to locate causative genes and susceptible loci were not always replicated. Cytogenomic methods (array CGH) have identified other regions of interest but studies have not shown consistent results, the resolution of arrays has varied and replication is uncommon. Whole-exome sequencing in non-syndromic POI kindreds has only recently begun, revealing mutations in the Stromal antigen 3 (STAG3), Synaptonemal complex central element 1 (SYCE1), minichromosome maintenance complex component 8 and 9 (MCM8, MCM9) and ATP-dependent DNA helicase homolog (HFM1) genes. Given the slow progress in candidate-gene analysis and relatively small sample sizes available for GWAS, family-based whole exome and whole genome sequencing appear to be the most promising approaches for detecting potential genes responsible for POI.CONCLUSIONTaken together, the cytogenetic, cytogenomic (array CGH) and exome sequencing approaches have revealed a genetic causation in ∼20–25% of POI cases. Uncovering the remainder of the causative genes will be facilitated not only by whole genome approaches involving larger cohorts in multiple populations but also incorporating environmental exposures and exploring signaling pathways in intragenic and interge...

show abstract

Section: Resultsmentioning

confidence: 99%

Genetics of primary ovarian insufficiency: new developments and opportunities

Qin

Jin

Simpson

et al. 2015

Hum. Reprod. Update

Self Cite

416

353

View full text Add to dashboard Cite

show abstract

“…The study suggested that as two of these variants, −210G > T and 530+6T > G, resulted in reduced mature protein production, the primordial to primary follicle transition will be altered, leading to accelerated follicle loss and contributing to the POF phenotype in these patients. 14 Additionally, a study conducted by Zhao et al 39 identified three novel SOHLH1 variants potentially causative to POF in 364 Chinese that were absent in 400 controls. However, replication studies in larger populations, especially those in different ethnicities, are required to validate a causative association of SOHLH1 and 2 variants with POF.…”

Section: Oocyte-specific Transcription Factorsmentioning

confidence: 99%

The genetics of premature ovarian failure: current perspectives

Chapman¹,

Cree²,

Shelling³

2015

IJWH

View full text Add to dashboard Cite

Premature ovarian failure (POF) is a common cause of infertility in women, characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women under the age of 40. Many genes have been identified over the past few years that contribute to the development of POF. However, few genes have been identified that can explain a substantial proportion of cases of POF. The unbiased approaches of genome-wide association studies and next-generation sequencing technologies have identified several novel genes implicated in POF. As only a small proportion of genes influencing idiopathic POF have been identified thus far, it remains to be determined how many genes and molecular pathways may influence idiopathic POF development. However, owing to POF’s diverse etiology and genetic heterogeneity, we expect to see the contribution of several new and novel molecular pathways that will greatly enhance our understanding of the regulation of ovarian function. Future genetic studies in large cohorts of well-defined, unrelated, idiopathic POF patients will provide a great opportunity to identify the missing heritability of idiopathic POF. The identification of several causative genes may allow for early detection and would provide better opportunity for early intervention, and furthermore, the identification of specific gene defects will help direct potential targets for future treatment.

show abstract

“…The same oocytespecific transcriptional factors have been identified to have established role in controlling the expression of genes involved follicular development also [105][106][107][108][110][111][112]. Furthermore, mutations in genes encoding these transcription factors are found to be associated with POI [52,62,68,[113][114][115][116][117][118][119]. This suggests an interconnected pathway between various facets of reproduction, viz.…”

Section: Genetic Factors Involved In Launch Of or And Their Putative mentioning

confidence: 97%