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The pathophysiology of diabetes
Published in Janet Titchener, Diabetes Management, 2020
Monogenic diabetes encompasses a heterogeneous group of diabetes that, as the name implies, are caused by a single gene defect or chromosomal abnormality within the β-cell resulting in impaired insulin secretion.16 Monogenic diabetes includes MODY (maturity-onset diabetes of the young), neonatal diabetes and mitochondrial diabetes. Multiple genetic mutations have now been identified resulting in many different types of monogenic diabetes. However, four types of monogenic diabetes, associated with mutations in the HNF1A, HNF1B, HNF4A and GCK genes, account for 90% of all cases.
Gynecological Developmental Abnormalities
Published in Linda Cardozo, Staskin David, Textbook of Female Urology and Urogynecology - Two-Volume Set, 2017
Melissa C. Davies, Sarah M. Creighton
The mAnAgement of this condition hAs chAnged in recent yeArs with the AdvAnces of reproductive technology. Previously, pAtients with cervicAl AtresiA were offered A totAl hysterectomy As complicAtions of recAnAlizing the cervix were common And A viAble pregnAncy wAs unlikely [26,42]. now the recommended treAtment options consist of either suppression of menses with preservAtion of the uterus for pregnAncy with reproductive AssistAnce or uterovAginAl AnAstomosis, which cAn now be performed lApAroscopicAlly [40]. There Are very little dAtA on fertility outcomes following uterovAginAl AnAstomosis; the lArgest study published stAted thAt the postoperAtive complicAtion rAte wAs low with only 22% requiring further surgery. Furthermore, they report six spontAneous pregnAncies in four of their pAtients [41]. Despite these encourAging results, it is importAnt to reAlize thAt the possibility of serious complicAtions exists And postoperAtive sepsis After uterovAginAl AnAstomosis hAs resulted in septic shock And deAth [43]. reproductive technology hAs AdvAnced to Allow these pAtients An opportunity to become pregnAnt And in vitro fertilizAtion techniques hAve Assisted these pAtients to become pregnAnt. There hAve been cAse reports of implAnting embryos trAnsmyometriAlly, which hAve resulted in A viAble pregnAncy [44,45]. In the lAtter cAse report, the pAtient underwent uterovAginAl cAnAlizAtion using Amniotic membrAne At the time of cesAreAn section [45]. one of the difficulties of these techniques is the mAnAgement of miscArriAge should it occur. CervicAl dilAtion And curettAge is often not An option As there mAy be no obvious cervix, or A smAll scArred stenosis. Therefore, most cAses would require A lApAroscopic or open removAl of the remnAnts of pregnAncy. one cAse report hAs used A conservAtive ApproAch of observAtion where the pAtient's b-hCG level wAs monitored with ultrAsound exAminAtion of the uterus [40]. Complex AnomAlies cAn be considered in two groups: AnAtomicAl or endocrine. This Allows us to distinguish between them bAsed upon the underlying cAuse rAther thAn the system Affected. Complex AnAtomicAl AnomAlies include the MAyer– rokitAnsky–Kuster–HAuser (MrKH) syndrome. CongenitAl Absence of the VAginA Agenesis of the vAginA occurs in ApproximAtely 1 in 5,000– 30,000 live femAle births [46,47]. It is commonly referred to As MrKH syndrome. In the mAjority of suffers, there is no discernAble vAginA present, while ApproximAtely 25% will hAve A short blind-ending pouch. This is Almost AlwAys AssociAted with An Absent or rudimentAry uterus. The kAryotype is XX And the ovAries Are normAl. AnomAlies of the Urinary trAct Are present in An estimAted 34% of pAtients, And spinAl AnomAlies Are found in 12% [48]. Although the etiology of this condition is unknown, there hAs been speculAtion As to A genetic cAuse And currently possible implicAted genes include HnF1b And members of the Wnt gene fAmily [49–51]. treAtment usuAlly involves formAtion of A vAginA. The preferred method for this is nonsurgicAl with the use of pressure
Clinical utility of chromosomal microarray analysis and whole exome sequencing in foetuses with oligohydramnios
Published in Annals of Medicine, 2023
Xiaomei Shi, Hongke Ding, Chen Li, Ling Liu, LiHua Yu, Juan Zhu, Jing Wu
We also identified a homozygous point variation c.199-10T > G in the SLC25A20 gene in case 4. Mutation of SLC25A20 is causative for Carnitine-acylcarnitine translocase deficiency (CACTD). Case 5 presented with oligohydramnios, hyperechogenic kidneys and enlarged kidneys. WES revealed a compound heterozygous mutation in PKHD1, a gene associated with PKD4. Case 6 had bilateral renal dysplasia and hypoplastic nasal bone in addition to oligohydramnios. WES revealed a compound heterozygous mutation in FRAS1. Mutations in the FRAS1 gene may cause Fraser syndrome. Case 7 carried a heterozygous mutation of (c.1406_1413dup8) in the HNF1B gene. Mutations in this gene cause renal cysts and diabetes syndrome. Ultrasound of this foetus showed severe oligohydramnios, bilateral renal dysplasia and an enlarged heart.
Retinoic acid signaling is critical for generation of pancreatic progenitors from human embryonic stem cells
Published in Growth Factors, 2023
Niloufer P. Dumasia, Aparna P. Khanna, Prasad S. Pethe
Next, to gain insights into the role of RA during the development of PE, we analyzed the expression of genes at stages PG, PF, and PE. qRT-PCR was performed to examine the stage-specific genes such as FOXA2, SOX17, HNF1β, HHEX, HNF4α, HNF6, and PDX1 upon RA modulation. At the PG stage, FOXA2 was upregulated by exogenous RA (Figure 3(A)). Addition of all-trans RA increased the expression of the PG tube markers HHEX and HNF4α at the PG stage (Figure 3(A)). Expression of these markers remained high throughout day 12 at the PF stage. In contrast to LE135-treated cells, treatment of the foregut endoderm progenitors with RA resulted in a marked increase in PDX1 transcripts. We observed a strong decrease in PDX1 mRNA upon inhibitor treatment. We found that HNF1β is also an RA-responsive gene early in pancreas development. Treatment of the differentiating cells with RA-inhibitor LE135 showed a strong reduction at the PG tube stage as compared to the addition of exogenous RA, which led to several fold increase in HNF1β mRNA at the same stage. During posterization of the gut tube, RA reduced HNF1β levels thereby allowing correct kinetic expression of these transcription factors.
A transcriptional regulatory network of HNF4α and HNF1α involved in human diseases and drug metabolism
Published in Drug Metabolism Reviews, 2022
Jianxin Yang, Xue Bai, Guiqin Liu, Xiangyang Li
The HNF1 family contains HNF1α and HNF1β. HNF1α is predominantly expressed in the human liver, followed by the ileum, renal cortex, testis, renal medulla, colon, subcutaneous fat, visceral fat, adrenal gland, aorta, and other tissues (Chen et al. 2020). The HNF1A gene on chromosome 12 encodes HNF1α. The protein structure of HNF1α consists of three domains (Figure 1), including an N-terminal dimerization binding domain, a DBD, and a C-terminal transactivation domain. The DBD is a highly conserved homeodomain with a 21-amino acid peptide inserted between α-helix 2 and 3 (Begum 2020). The N-terminal is a conserved POUs domain unique to the POU family, the C-terminal is a traditional POUh homeodomain, and a peptide connects the POUs and POUh domains. Unlike other POU TFs, HNF1α and HNF1β bind to DNA only in the dimer form, thus greatly increasing the complexity and diversity of their functions.