Department of Biomedical Sciences, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Ghana.
Department of Physician Assistant Studies, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Ghana.
Eur J Med Genet. 2021 Mar;64(3):104158. doi: 10.1016/j.ejmg.2021.104158. Epub 2021 Feb 4.
Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome is a sex development disorder that affects 1 in every 4500 46, XX live births. At least a subset of MRKH syndrome is genetically related to which various candidate genes have been identified. The growth regulation by estrogen in breast cancer 1-like gene (GREB1L) is an androgen-regulated gene reported to be a co-activator of the retinoic acid receptor gene (RAR). Thus expression levels of GREB1L have implications on renal system cellular differentiation, morphogenesis, and homeostasis in vertebrates. Variants of GREB1L have been reported in familial and sporadic MRKH Syndrome and more importantly, in a three-generation family ofMRKH syndrome propositae. Much the same way, Mutants of GREB1L have also been identified in isolated bilateral renal agenesis and deafness both of which are extra-genital tract anomalies in MRKH type 2. Again, renal agenesis transgenic mice have been produced from an E13.5 CRISPR/cas9 GREB1L mutagenesis. Though no GREB1L mutation has been reported in cardiac malformation, there is evidence that GREB1L is involved in ventricular development. Here, we intorigate evidence that projects GREB1L as a candidate gene of Mayer-Rokitansky-Küster-Hauser Syndrome and propose that functional validation analysis to that effect is imparative.
Mayer-Rokitansky-Küster-Hauser (MRKH) 综合征是一种性发育障碍，影响每 4500 名 46,XX 活产儿中的 1 名。至少一部分 MRKH 综合征与各种候选基因有关，这些候选基因已经被确定。雌激素在乳腺癌 1 样基因（GREB1L）中的生长调节作用是一种雄激素调节基因，据报道是维甲酸受体基因（RAR）的共激活因子。因此，GREB1L 的表达水平对脊椎动物的肾脏系统细胞分化、形态发生和内稳态有影响。已经在家族性和散发性 MRKH 综合征以及更重要的是在三代 MRKH 综合征先证者家族中报道了 GREB1L 的变体。同样，GREB1L 的突变体也在孤立的双侧肾发育不全和耳聋中被鉴定出来，这两种都是 MRKH 型 2 的生殖道外异常。此外，已经从 E13.5 CRISPR/cas9 GREB1L 诱变产生了肾发育不全的转基因小鼠。虽然在心脏畸形中没有报道 GREB1L 突变，但有证据表明 GREB1L 参与心室发育。在这里，我们研究了 GREB1L 作为 Mayer-Rokitansky-Küster-Hauser 综合征候选基因的证据，并提出有必要对此进行功能验证分析。
