Lhx4

OBJECTIVE: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. MATERIALS AND METHODS: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing...

PURPOSE: Congenital hypopituitarism (CH) disorders are phenotypically variable. Variants in multiple genes are associated with these disorders, with variable penetrance and inheritance. METHODS: We screened a large cohort (n=1,765) of patients with or at risk of CH using Sanger sequencing, selected according to phenotype, and conducted next generation sequencing (NGS) in 51 families within our cohort. We report the clinical, hormonal and neuroradiological phenotypes of patients with variants in known genes associated with CH...

INTRODUCTION: Among children born small for gestational age, 10-15% fail to catch up and remain short (SGA-SS). The underlying mechanisms are mostly unknown. We aimed to decipher genetic aetiologies of SGA-SS within a large single-centre cohort. METHODS: Out of 820 patients treated with growth hormone (GH), 256 were classified as SGA-SS (birth length and/or birth weight <-2 SD for gestational age and life-minimum height <-2.5 SD). Those with the DNA triplet available (child and both parents) were included in the study (176/256)...

BACKGROUND: LIM homeobox transcription factor 4 (LHX4) is a promising candidate gene for mammalian reproductive traits. LHX4 polymorphism has previously been associated with phenotypic traits in goats and cattle. However, there have been no LHX4 gene polymorphisms identified in Awassi sheep. Therefore, this study investigated the effects of the LHX4 polymorphism on reproductive hormones, growth hormones, and prolactin in Awassi ewes. METHODS AND RESULTS: A total of 232 ewes between the ages of 3 and 4 years were selected for this study (123 single-progeny ewes and 109 twin-producing ewes)...

Combined pituitary hormone deficiency (CPHD) is characterized by deficiency of growth hormone and at least one other pituitary hormone. Pathogenic variants in more than 30 genes expressed during the development of the head, hypothalamus, and/or pituitary have been identified so far to cause genetic forms of CPHD. However, the etiology of around 85% of the cases remains unknown. The aim of this study was to unveil the genetic etiology of CPHD due to congenital hypopituitarism employing whole exome sequencing (WES) in two newborn patients, initially tested and found to be negative for PROP1 , LHX3 , LHX4 and HESX1 pathogenic variants by Sanger sequencing and for copy number variations by MLPA...

OBJECTIVE: To identify and characterize a novel deletion at the LHX4 gene locus in a proband with growth hormone deficiency (GHD). METHODS: Long range polymerase chain reaction (PCR) amplification was used to confirm the suspected deletion and to identify the rough locations of the end points. Sanger sequencing was carried out to identify the exact end points of the deletion. RESULTS: Suspected deletion was confirmed via long range PCR amplification...

LIM homeodomain (LIM-HD) family genes are transcription factors that play crucial roles in a variety of functions during embryonic development. The activities of the LIM-HD proteins are regulated by the co-regulators LIM only (LMO) and LIM domain-binding (LDB). In the mouse genome, there are 13 LIM-HD genes (Lhx1-Lhx9, Isl1-2, Lmx1a-1b), 4 Lmo genes (Lmo1-4), and 2 Ldb genes (Ldb1-2). Amongst these, Lhx1 is required for the development of the müllerian duct epithelium and the timing of the primordial germ cell migration...

Hypertrophic chondrocytes and their specific marker, the type X collagen gene ( Col10a1 ), are critical components of endochondral bone formation during skeletal development. We previously found that Runx2 is an indispensable mouse Col10a1 gene regulator and identified many other transcription factors (TFs) that potentially interact with the 150-bp Col10a1 cis-enhancer. However, the roles of these candidate TFs in Col10a1 expression and chondrocyte hypertrophy have not been elucidated. Here, we focus on 32 candidate TFs recently identified by analyzing the 150-bp Col10a1 enhancer using the transcription factor affinity prediction (TRAP) program...

Homeobox genes encode transcription factors controlling development; however, a number of homeobox genes are expressed postnatally specifically in melatonin-producing pinealocytes of the pineal gland and photoreceptors of the retina along with transcripts devoted to melatonin synthesis and phototransduction. Homeobox genes regulate melatonin synthesis in pinealocytes, but some homeobox genes also seem to be involved in regulation of retinal phototransduction. Due to the lack of photoreceptor models, we here introduce the rat pinealocyte culture as an in vitro model for studying retinal phototransduction...

OBJECTIVE: To explore unusual association between Turner Syndrome (TS) and Hypopituitarism in a Tunisian cohort. METHODS: We reported 6 patients with TS associated to Hypopituitarism, including three familial cases except the fourth sister who showed only a TS phenotype. Biochemical analysis, resonance magnetic imaging and cytogenetic analyses were performed. RESULTS: The average age of our patients was 17.2 years (11-31 years). They were all referred for short stature and pubertal delay, except for the fourth sister who presented spontaneous puberty with the integrity of the pituitary axis and the presence of an X ring chromosome...

PURPOSE: Congenital hypopituitarism (CH) can present in isolation or with other birth defects. Mutations in multiple genes can cause CH, and the use of a genetic screening panel could establish the prevalence of mutations in known and candidate genes for this disorder. It could also increase the proportion of patients that receive a genetic diagnosis. METHODS: We conducted target panel genetic screening using single-molecule molecular inversion probes sequencing to assess the frequency of mutations in known hypopituitarism genes and new candidates in Argentina...

LIM homeobox 4 (LHX4) is expressed in the photoreceptors (PRs) of the outer nuclear layer (ONL) and bipolar cells (BCs) of the inner nuclear layer (INL) in mouse and chicken retina. It regulates the subtype-specific development of rod BCs and cone BCs in the mouse retina. However, no report has been published on its expression and function in the zebrafish retina. In this study, we assessed the expression of Lhx4 using in situ hybridization (ISH) technique and explored its role in zebrafish (Danio rerio) retinal development via morpholino (MO) technology...

CONTEXT: The international GENHYPOPIT network collects phenotypical data and screens genetic causes of non-acquired hypopituitarism. AIMS: To describe main phenotype patterns and their evolution through life. DESIGN: Patients were screened according to their phenotype for coding sequence variations in 8 genes: HESX1, LHX3, LHX4, PROP1, POU1F1, TBX19, OTX2 and PROKR2. RESULTS: Among 1213 patients (1143 index cases), the age of diagnosis of hypopituitarism was congenital (24%), in childhood (28%), at puberty (32%), in adulthood (7...

Retinal bipolar cells (BCs) connect with photoreceptors and relay visual information to retinal ganglion cells (RGCs). Retina-specific deletion of Lhx4 in mice results in a visual defect resembling human congenital stationary night blindness. This visual dysfunction results from the absence of rod bipolar cells (RBCs) and the loss of selective rod-connecting cone bipolar cell (CBC) subtypes and AII amacrine cells (ACs). Inactivation of Lhx4 causes the apoptosis of BCs and cell fate switch from some BCs to ACs, whereas Lhx4 overexpression promotes BC genesis...

Objective: To observe the changes of LHX4 and DIS3L mRNA and protein expression in Nthy-ori-3-1 cells after the treatment of thyroid disruptor p , p '-DDE. Methods: Nthy-ori-3-1 cells in logarithmic growth phase were treated with 0, 0.5, 1.0, 2.0 and 5.0 μg/ml p , p '-DDE solution. The growth state and morphology of the cells were observed by microscope. The mRNA levels of LHX4 and DIS3L were detected by real-time fluorescent quantitative PCR, and the protein expression levels of LHX4 and DIS3L were detected by Western blot...

Pituitary stalk interruption syndrome (PSIS) is a type of congenital malformation of the anterior pituitary, which leads to isolated growth hormone deficiency or multiple hypothalamic-pituitary deficiencies. Many genetic factors have been explored, but they only account for a minority of the genetic aetiology. To identify novel PSIS pathogenic genes, we conducted whole-exome sequencing with 59 sporadic PSIS patients, followed by filtering gene panels involved in pituitary development, holoprosencephaly and midline abnormality...

Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome...

Background: The mutation frequencies of pituitary transcription factors genes in patients with combined pituitary hormone deficiencies (CPHD) vary substantially between populations. However, apart from PROP1 the mutation rate of other genes is low and for almost half of the patients with CPHD the routine sequencing of known genes is unsuccessful in the identification of genetic causes. Methods: A cohort of 66 sporadic and nine familial CPHD cases (80 patients in total) were subjected to initial testing of the genes PROP1, POU1F1, LHX3, LHX4 , and HESX1 using a targeted gene panel and MLPA...

Cell fusion occurs when several cells combine to form a multinuclear aggregate (syncytium). In human placenta, a syncytialized trophoblast (syncytiotrophoblast) layer forms the primary interface between maternal and fetal tissue, facilitates nutrient and gas exchange, and produces hormones vital for pregnancy. Syncytiotrophoblast development occurs by differentiation of underlying progenitor cells called cytotrophoblasts, which then fuse into the syncytiotrophoblast layer. Differentiation is associated with chromatin remodeling and specific changes in gene expression mediated, at least in part, by histone acetylation...

Genetic disorders have been shown to co-occur in individual patient. A Thai boy with features of osteogenesis imperfecta (OI) and combined pituitary hormone deficiency (CPHD) was identified. The causative mutations were investigated by whole exome and Sanger sequencing. Pathogenicity and pathomechanism of the variants were studied by luciferase assay. The proband was found to harbor a novel de novo heterozygous missense mutation, c.1531G > T (p.G511C), in COL1A2 leading to OI and a heterozygous missense variant, c...