Number Of Repeats Research Articles

Rest-activity disturbances and light exposure in myotonic dystrophy type 1 patients with apathy: An exploratory study using actigraphy

BackgroundRest-activity rhythm disturbances have been reported in myotonic dystrophy type 1 (DM1) but no study has assessed its relationship with apathy and light exposure using actigraphy. MethodsThirty-three DM1 patients wore an actigraph for two consecutive weeks. The Lille Apathy Rating Scale was used to assess apathy. Actigraphy was used to characterize sleep, activity, and light exposure and nonparametric analysis was performed to characterize intraday variability (IV), interday stability (IS), least active five-hour period (L5), most active ten-hour period (M10), and relative amplitude (RA). ResultsApathy was found in 42.4% of patients. Patients with apathy have a larger number of CTG repeat than those without (774 vs 381, p<0.01) Also, patients with apathy had higher IV values (0.98 vs 0.69, p<0.001) as well as lower IS (0.34 vs 0.47, p<0.05), RA (0.65 vs 0.83, p<0.05), and M10 (182.6 vs 493.8, p<0.001) values compared to patients without apathy. In addition, DM1 patients with apathy were exposed to less bright light (≥1000 lux) (41.4 vs 141.2 minutes p<0.01) than patients without. No difference was observed relatively to sleep quality and quantity. ConclusionsDaytime activity levels and bright light exposure were significantly lower in DM1 patients with apathy versus those without. The more fragmented, less stable, and lower amplitude rest-activity rhythm of DM1 patients with apathy, as revealed by non parametric analysis, can be partly ascribed to reduced daylight exposure. The use of bright light therapy as well as physical activity interventions should be explored to help prevent or reduce apathy levels in DM1.

Development of Expressed Sequence Tag–Simple Sequence Repeat Markers Related to the Salt-Stress Response of Kenaf (Hibiscus cannabinus)

Kenaf is one of the most important natural cannabis plants. Molecular marker-assisted breeding is vital for accelerating the breeding process of kenaf. However, the number of kenaf markers is insufficient for molecular marker-assisted breeding. Using transcriptome sequencing data for salt-stressed kenaf plants, the number and distribution of simple sequence repeats (SSRs) and single nucleotide variations (SNVs) in the expressed sequences were determined. The objectives of this study were to elucidate the sequence variations in kenaf genes expressed in response to salt stress and to identify stable and dependable molecular markers. Primers were designed for SSR loci and then EST-SSR molecular markers were generated. The subsequent analyses revealed that 30.50% of the unigenes contained SSR motifs, most of which were single nucleotides followed by trinucleotides and dinucleotides. The unigenes containing SSRs were mostly associated with kenaf salt tolerance. Additionally, 10,483 SNVs were detected in contig sequences. Of the 3995 differentially expressed genes encoding interacting proteins, 1297 contained SSRs. Most of these genes were associated with metabolic pathways (e.g., 03000 transcription factors, B09132 signal transduction, and 04122 sulfur relay system). We designed 20 pairs of EST-SSR primers to genotype 30 kenaf varieties (lines), of which 9 primer pairs were ideal for genotyping (e.g., 1 highly polymorphic marker and 2 moderately polymorphic markers). The primer pairs designed for the EST-SSR markers in the kenaf genome may be useful SSR molecular markers for future research on kenaf. The verified polymorphic markers may be applicable to the molecular marker-assisted breeding of salt-tolerant kenaf varieties.

Notch1 is involved in cell proliferation and neuronal differentiation in the HVC of zebra finch (Taeniopygia guttata)

Significant sex differences are found in songbirds’ song control nuclei and their controlled song behaviors. To elucidate the underlying mechanisms, we explored the role of Notch1 during the development of the high vocal centre (HVC) and song learning in zebra finch. Our study first found that Notch1 positive cells were distributed in HVC with female-biased densities at posthatching day (PHD) 15, but male-biased at PHD 45 and adult. There were about 60 putative oestrogen-responsive elements within 2.5 kb upstream of Notch1, and Notch1 mRNA in the explants that contained the developing male HVC was significantly increased after estrogen addition into the cultured medium for 48 h. After injecting Notch1-interfering lentivirus into the male or female HVC at PHD 15, cell proliferation was significantly promoted in the ventricle zone overlying the HVC at PHD 23. In addition, neuronal differentiation towards Hu+ /BrdU+ at PHD 31, mature neurons (NeuN+/BrdU+) including those projecting to RA in HVC and the sizes of HVC and RA at adult increased significantly after Notch1-interfering lentiviruses were injected into the male HVC at PHD 15. However, the above measurements decreased, following the injection of the lentiviruses expressing Notch intracellular domain (NICD). Finally, the repeat numbers of syllables ‘b′ or ‘c′ of learned songs changed after the injection of Notch1-interfering or NICD-expressing lentiviruses into the HVC at PHD15. Our study suggests that Notch1 is related to the development of HVC and song learning in the zebra finch.

Comparison of the evolutionary patterns of DNA repeats in ancient and young invertebrate species flocks of Lake Baikal.

DNA repeat composition of low coverage (0.1-0.5) genomic libraries of four amphipods species endemic to Lake Baikal (East Siberia) and four endemic gastropod species of the fam. Baicaliidae have been compared to each other. In order to do so, a neighbor joining tree was inferred for each quartet of species (amphipods and mollusks) based on the ratio of repeat classes shared in each pair of species. The topology of this tree was compared to the phylogenies inferred for the same species from the concatenated protein-coding mitochondrial nucleotide sequences. In all species analyzed, the fraction of DNA repeats involved circa half of the genome. In relatively more ancient amphipods (most recent common ancestor, MRCA, existed approximately sixty millions years ago), the most abundant were species-specific repeats, while in much younger Baicaliidae (MRCA equal to ca. three millions years) most of the DNA repeats were shared among all four species. If the presence/absence of a repeat is regarded as a separate independent trait, and the ratio of shared to total numbers of repeats in a species pair is used as the measure of distance, the topology of the NJ tree is the same as the quartet phylogeny inferred for the mitogenomes protein coding nucleotide sequences. Meanwhile, in each group of species, a substantial number of repeats were detected pointing to the possibility of non-neutral evolution or a horizontal transfer between species occupying the same biotope. These repeats were shared by non-sister groups while being absent in the sister genomes. On the other hand, in such cases some traits of ecological significance were also shared.

&lt;i&gt;In silico&lt;/i&gt; analysis of genomes of Bacillus anthracis strains belonging to major genetic lineages

Introduction. The global phylogenetic population structure of Bacillus anthracis is represented by major genetic lineages (A, B and C) with nonuniform distribution of isolates, which still cannot be explained. Identification of characteristics of genomes of strains from three lineages, which can affect their spread, is of high importance.&#x0D; The aim of the study is to explore genomic characteristics of different genetic lineages, which may have an effect on their distribution, by using the in silico analysis of a representative subset of B. anthracis strains.&#x0D; Materials and methods. The whole-genome sequences of 49 B. anthracis strains and Bacillus cereus biovar anthracis CI strain were studied. The in silico analysis was performed to identify polymorphisms using BLASTn, MEGA X, Tandem Repeat Finder, Parsnp the Harvest Suite software.&#x0D; Results. The genome variability depended on single nucleotide polymorphisms, single-nucleotide repeats, number of tandem repeats, substitutions and indels. In strains from lineages B and C, they outnumbered 1.613.4 times and in the B. cereus biovar anthracis strain 5150 times those in B. anthracis strains from lineage A. Significant substitutions in housekeeping genes and pathogenicity factor genes caused changes in amino acid sequences in proteins significantly more frequently in B. anthracis strains from major lineages B and C.&#x0D; Based on the molecular typing and a multi-virulence-locus sequence typing analysis (MVLST) with a discrimination index of 0.9633, strains were classified into three major genetic lineages including groups different from the canonical group.&#x0D; Conclusion. The distinctive feature of B. anthracis genomes is that they have a larger number of significant nucleotide substitutions in pathogenicity factor genes and housekeeping genes of strains belonging to major lineages B and C compared to lineage A. Changes in proteins encoded by them can cause differences in ecological adaptation and in prevalence, which are higher in strains of lineage A. MVLST having a high discriminating capacity can be used as an additional method to B. anthracis molecular typing.

Blockade of MIF biological activity ameliorates house dust mite-induced allergic airway inflammation in humanized MIF mice.

Macrophage migration inhibitory factor (MIF) expression is controlled by a functional promoter polymorphism, where the number of tetranucleotide repeats (CATTn ) corresponds to the level of MIF expression. To examine the role of this polymorphism in a pre-clinical model of allergic asthma, novel humanized MIF mice with increasing CATT repeats (CATT5 and CATT7 ) were used to generate a physiologically relevant scale of airway inflammation following house dust mite (HDM) challenge. CATT7 mice expressing high levels of human MIF developed an aggressive asthma phenotype following HDM challenge with significantly elevated levels of immune cell infiltration, production of inflammatory mediators, goblet cell hyperplasia, subepithelial collagen deposition, and airway resistance compared to wild-type controls. Importantly the potent MIF inhibitor SCD-19 significantly mitigated the pathophysiology observed in CATT7 mice after HDM challenge, demonstrating the fundamental role of endogenous human MIF expression in the severity of airway inflammation in vivo. Up to now, there are limited reproducible in vivo models of asthma airway remodeling. Current asthma medications are focused on reducing the acute inflammatory response but have limited effects on airway remodeling. Here, we present a reproducible pre-clinical model that capitulates asthma airway remodeling and suggests that in addition to having pro-inflammatory effects MIF may play a role in driving airway remodeling.

Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation

IntroductionThe incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). MethodsRetrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5–35), premutation (36–50), protomutation (51–80), small expansions (81–150), intermediate expansions (151–1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5–50 CTG repeats), mild form or asymptomatic (51–150), classical form (151–1000), and severe form (> 1000). ResultsThe incidence of DM1 was 20.61 cases per million person-years (95% CI, 19.59–21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = –0.547; 95% CI, –0.610 to –0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. ConclusionsThe incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

Bilayer Hydrogel Composed of Elastin-Mimetic Polypeptides as a Bio-Actuator with Bidirectional and Reversible Bending Behaviors.

Biologically derived hydrogels have attracted attention as promising polymers for use in biomedical applications because of their high biocompatibility, biodegradability, and low toxicity. Elastin-mimetic polypeptides (EMPs), which contain a repeated amino acid sequence derived from the hydrophobic domain of tropoelastin, exhibit reversible phase transition behavior, and thus, represent an interesting starting point for the development of biologically derived hydrogels. In this study, we succeeded in developing functional EMP-conjugated hydrogels that displayed temperature-responsive swelling/shrinking properties. The EMP-conjugated hydrogels were prepared through the polymerization of acrylated EMP with acrylamide. The EMP hydrogel swelled and shrank in response to temperature changes, and the swelling/shrinking capacity of the EMP hydrogels could be controlled by altering either the amount of EMP or the salt concentration in the buffer. The EMP hydrogels were able to select a uniform component of EMPs with a desired and specific repeat number of the EMP sequence, which could control the swelling/shrinking property of the EMP hydrogel. Moreover, we developed a smart hydrogel actuator based on EMP crosslinked hydrogels and non-crosslinked hydrogels that exhibited bidirectional curvature behavior in response to changes in temperature. These thermally responsive EMP hydrogels have potential use as bio-actuators for a number of biomedical applications.

Estimating Census Tract House Price Indexes: A New Spatial Dynamic Factor Approach

AbstractGeographically and temporally granular housing price indexes are difficult to construct. Data sparseness, in particular, is a limiting factor in their construction. A novel application of a spatial dynamic factor model allows for the construction of census tract level indexes on a quarterly basis while accommodating sparse data. Specifically, we augment the repeat sales model with a spatial dynamic factor model where loadings on latent trends are allowed to follow a spatial random walk thus capturing useful information from similar neighboring markets. The resulting indexes display less noise than similarly constructed non-spatial indexes and replicate indexes from the traditional repeat sales model in tracts where sufficient numbers of repeat sales pairs are available. The granularity and frequency of our indexes is highly useful for policymakers, homeowners, banks and investors.

Comparative analysis of mitochondrial genomes of Schisandra repanda and Kadsura japonica.

The family Schisandraceae is a basal angiosperm plant group distributed in East and Southeast Asia and includes many medicinal plant species such as Schisandra chinensis. In this study, mitochondrial genomes (mitogenomes) of two species, Schisandra repanda and Kadsura japonica, in the family were characterized through de novo assembly using sequencing data obtained with Oxford Nanopore and Illumina sequencing technologies. The mitogenomes of S. repanda were assembled into one circular contig (571,107 bp) and four linear contigs (10,898-607,430 bp), with a total of 60 genes: 38 protein-coding genes (PCGs), 19 tRNA genes, and 3 rRNA genes. The mitogenomes of K. japonica were assembled into five circular contigs (211,474-973,503 bp) and three linear contigs (8,010-72,712 bp), with a total of 66 genes: 44 PCGs, 19 tRNA genes, and 3 rRNA genes. The mitogenomes of the two species had complex structural features with high repeat numbers and chloroplast-derived sequences, as observed in other plant mitogenomes. Phylogenetic analysis based on PCGs revealed the taxonomical relationships of S. repanda and K. japonica with other species from Schisandraceae. Finally, molecular markers were developed to distinguish between S. repanda, K. japonica, and S. chinensis on the basis of InDel polymorphisms present in the mitogenomes. The mitogenomes of S. repanda and K. japonica will be valuable resources for molecular and taxonomic studies of plant species that belong to the family Schisandraceae.

Determinants of Hand Washing with Soap (HWWS) in Rural Communities: Cross Sectional Study in Manggarai Regency East Nusa Tenggara Indonesia

Hand Washing With Soap (HWWS) behavior is a simple thing that can be done to inhibit the transmission of disease from the source of infection. Not much is known with certainty about the determinants of community handwashing behavior as a basis for promoting handwashing behavior. The research aims to identify the various determinants of HWWS behavior in the rural community, the results of which can be considered for designing the promotion of HWWS behavior in rural community and economically vulnerable groups.&#x0D; A total of 52 villages as survey locations, interviews and observations were carried out on 168 household heads who were determined by purposive random sampling with the inclusion criteria of having toddlers, and the house is on the edge of a river / beach. Univariate data processing to describe the characteristics of respondents and bivariate analysis to describe the relationship between the various HWWS behavior variables.&#x0D; The results of the study showed that the majority of the community already had HWWS facilities and were around the house where they lived. Critical times for community hand washing behavior are when hands are dirty, after feeding livestock and before eating. There is no difference between the determinants of HWWS behavior with education and with household categories based on the number of repeaters. Health cadres and local health workers dominate the sources of information obtained by the community regarding HWWS behavior.&#x0D; The implication of the results of this study is that the promotion of HWWS behavior in the community needs to consider non-health messages such as HWWS carried out when hands are dirty, after feeding livestock and before eating. In addition to inhibiting the spread of diseases that are transmitted through hands, the goal of HWWS behavior is also. In addition, health cadres and health workers are very important as a channel for conveying education about HWWS behavior in the community, in addition to the use of social media.

Pharmacogenomics and the Concept of Personalized Medicine for the Management of Hypertension

Pharmacogenomics and the Concept of Personalized Medicine for the Management of Hypertension

Amaranth Genomic Resource Database: an integrated database resource of Amaranth genes and genomics.

Amaranth (Amaranthus L.) is native to Mexico and North America, where it was cultivated thousands of years ago, but now amaranth is grown worldwide. Amaranth is one of the most promising food crops with high nutritional value and belongs to the family Amaranthaceae. The high-quality genome assembly of cultivated amaranth species (A. hypochondriacus, A. cruentus) and wild/weedy species (A. tuberculatus, A. hybridus, and A. palmeri) has already been reported; therefore, we developed an Amaranth Genomic Resource Database (AGRDB) to provide access to all the genomic information such as genes, SSRs, SNPs, TFs, miRNAs, and transporters in one place. The AGRDB database contains functionally annotated gene information with their sequence details, genic as well as genomic SSRs with their three sets of primers, transcription factors classified into different families with their sequence information and annotation details, putative miRNAs with their family, sequences, and targeted gene details, transporter genes with their superfamily, trans-membrane domain details, and details of genic as well as nongenic SNPs with 3' and 5' flanking sequence information of five amaranth species. A database search can be performed using the gene ID, sequence ID, sequence motif, motif repeat, family name, annotation keyword, scaffold or chromosome numbers, etc. This resource also includes some useful tools, including JBrowse for the visualization of genes, SSRs, SNPs, and TFs on the respective amaranth genomes and BLAST search to perform a BLAST search of the user's query sequence against the amaranth genome as well as protein sequences. The AGRDB database will serve as a potential platform for genetic improvement and characterization of this futuristic crop. The AGRDB database will be accessible via the link: http://www.nbpgr.ernet.in:8080/AmaranthGRD/.

Modified Smoluchowski Rate Equations for Aggregation and Fragmentation in Finite Systems.

Protein self-assembly into supramolecular structures is important for cell biology. Theoretical methods employed to investigate protein aggregation and analogous processes include molecular dynamics simulations, stochastic models, and deterministic rate equations based on the mass-action law. In molecular dynamics simulations, the computation cost limits the system size, simulation length, and number of simulation repeats. Therefore, it is of practical interest to develop new methods for the kinetic analysis of simulations. In this work we consider the Smoluchowski rate equations modified to account for reversible aggregation in finite systems. We present several examples and argue that the modified Smoluchowski equations combined with Monte Carlo simulations of the corresponding master equation provide an effective tool for developing kinetic models of peptide aggregation in molecular dynamics simulations.

The association of cytosine-adenine-guanine repeat polymorphism in the androgen receptor gene with nodulocystic acne in Egyptian patients

Background: The role of androgens in acne pathophysiology has been supported by long-standing clinical and experimental observations. Methods: Genotyping for the androgen receptor gene was performed by PCR-based fragment length analysis, aiming to investigate cytosine-adenine-guanine (CAG) repeat polymorphism in Egyptian nodulocystic acne patients to clarify its relevance to the pathogenesis. Detailed frequency of CAG repeats number in patients and control groups, in 25 males and 25 females and Comparison of CAG repeat number regarding demographic and clinical characteristics was performed. Results: It was found that females had a higher frequency of longer CAG repeats compared to males, while in control group there was an even distribution of CAG number repeats in both females and males. Male and female acne patients had significantly lower number of CAG repeats compared to controls with statistically significant difference (p≤0.05). Comparison of CAG repeat number regarding demographic and clinical characteristics revealed no significant correlation or association with patients’ age, duration of acne, onset or course of the disease. Conclusions: These findings support the hypothesis that CAG repeats number affects AR activity, therefore, acne development and severity. Moreover, analysis of CAG repeats number in acne patients can be of considerable importance in the treatment strategy, indicating the role of antiandrogen therapy in acne patients.

Clinical characteristics of different forms of myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is one of the most common neuromuscular diseases with an autosomal dominant type of inheritance associated with expansion in the DMPK gene. A distinctive feature of the disease is the presence of muscle symptoms and multisystemic. Depending on the age of onset and the number of CTG repeats, there are congenital, infantile, juvenile, classic (adult) form and a form with a late onset. Each form is characterized by its own features of the onset, course of the disease, heterogeneity of clinical manifestations, which makes it difficult to make a timely diagnosis. Increasing the awareness of physicians of all specialties about the nature of the course of various forms will make it possible to diagnose MD1 at an earlier stage, improve the prognosis and quality of life of patients. The article provides a literature review that demonstrates the spectrum of clinical manifestations in various forms of MD1.

The sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem Repeats

Microsatellites, or Short Tandem Repeats (STRs), are subject to frequent length mutations that involve the loss or gain of an integer number of repeats. This work aimed to investigate the correlation between STRs’ specific repetitive motif composition and mutational dynamics, specifically the occurrence of single- or multistep mutations. Allelic transmission data, comprising 323,818 allele transfers and 1,297 mutations, were gathered for 35 Y-chromosomal STRs with simple structure. Six structure groups were established: ATT, CTT, TCTA/GATA, GAAA/CTTT, CTTTT, and AGAGAT, according to the repetitive motif present in the DNA leading strand of the markers. Results show that the occurrence of multistep mutations varies significantly among groups of markers defined by the repetitive motif. The group of markers with the highest frequency of multistep mutations was the one with repetitive motif CTTTT (25% of the detected mutations) and the lowest frequency corresponding to the group with repetitive motifs TCTA/GATA (0.93%). Statistically significant differences (α = 0.05) were found between groups with repetitive motifs with different lengths, as is the case of TCTA/GATA and ATT (p = 0.0168), CTT (p < 0.0001) and CTTTT (p < 0.0001), as well as between GAAA/CTTT and CTTTT (p = 0.0102). The same occurred between the two tetrameric groups GAAA/CTTT and TCTA/GATA (p < 0.0001) – the first showing 5.7 times more multistep mutations than the second. When considering the number of repeats of the mutated paternal alleles, statistically significant differences were found for alleles with 10 or 12 repeats, between GATA and ATT structure groups. These results, which demonstrate the heterogeneity of mutational dynamics across repeat motifs, have implications in the fields of population genetics, epidemiology, or phylogeography, and whenever STR mutation models are used in evolutionary studies in general.

P-714 Clinical utility of FMR1 screening: risk factor or monogenic cause for POI

Abstract Study question Is there a risk factor association or a monogenic relationship between FMR1 premutation and developing Fragile X-associated primary ovarian insufficiency (FXPOI)? Summary answer There is an association between FMR1 premutation and FXPOI rather than a monogenic relationship, which is highly dependent on ethnicity. What is known already Among the 40 genes involved in primary ovarian insufficiency (POI), identified in our recent systematic review (Van Der Kelen et al., 2022), the FMR1 premutation is considered as the most common cause of POI. A premutation in the FMR1 gene is defined as a CGG trinucleotide repeat length between 55 and 200 in the 5′ untranslated region. The term FXPOI is used for women with premutation in FMR1 who have a loss of normal function of the ovaries before the age of 40. There is conflicting evidence about the relationship between POI and length of premutation FMR1 alleles. Study design, size, duration Curated publications identified in PubMed and Web of Science on genetics of human female infertility and sex development by using the MESH terms, key words and inclusion/exclusion criteria described in our comprehensive systematic review were subjected to screening for “FMR1 gene.” The articles included cover a period from 1988 to the 1st of November 2021. Participants/materials, setting, methods A total of 161 publications in PubMed and 61 unique publications in Web of Science were identified, and subsequently screened for triplet expansion, primary ovarian insufficiency, and/or early menopause. Of these, 56 papers were selected, excluding publications exclusively on males as well as studies on non-human species, pediatric cases, reviews, and expression studies. The study and control groups repeat numbers, ethnicity, and conclusions in the article are listed. Main results and the role of chance Expansion in CGG trinucleotide repeat length happens at female meiosis and the risk for expansion increases with an increasing number of CGG repeats. There is an intermediate zone between 45 and 55 CGG repeats when the allele may be stable or unstable. Among 56 publications, 54 describing FMR1 triplet repeat size in women with POI, 34 were studying only the women with POI (observational) while 20 were including also control group (comparative). 2 publications were meta-analyses in which 13 and 11 case control studies were included respectively, 5 studies being in common. POI-associated premutations showed a wide range of repeat sizes. Women carrying midsize range repeats (&amp;gt;70-&amp;lt;100) potentially have a higher risk for POI compared to the general population. In recent decades, population-based screenings have indicated that FMR1 premutations are not as prevalent in women with ovarian insufficiency as previous estimates have suggested, but they still represent a substantial cause of POI. When present, the number of AGG interruptions and the size of uninterrupted CGG repeats are directly correlated with the ovarian reserve. No increased risk of POI associated with a premutation was reported among populations of non-European descent, such as the Han Chinese, Indian, and Jordan populations. Limitations, reasons for caution Available reports are difficult to compare because the ethnicity and number of patients analyzed, availability of clinical data and the quality of results are different in each study. Additionally, an effect of X-inactivation in POI women with premutation was not studied. Wider implications of the findings Owing to the low penetrance and a molecular mechanism that has not yet been fully elucidated, the clinical utility of FMR1 screening in women with reduced ovarian reserve needs further investigation before clinical implication. Trial registration number N/A

1619-P: Creation of a Mouse Model That Phenocopies Human MODY8—A Valuable Tool to Interrogate Exocrine–Endocrine Cross Talk

Despite the intimate anatomical relationship between the two compartments of the pancreas, little is known about the biological components mediating the exocrine-endocrine communication in regulating glucose homeostasis. Maturity-onset diabetes of the young, type 8 (MODY8) is a dominantly inherited autosomal form of monogenic diabetes, caused by heterozygous mutations in the carboxy ester lipase (CEL) gene expressed in acinar cells. MODY8 is characterized by chronic pancreatitis (CP) and exocrine dysfunction from childhood, followed by diabetes in adulthood. Heterozygous MODY8 mice develop CP but are normoglycemic. Here, we report a refined mouse model that bears the mutation present in MODY8 patients on one allele, and the humanized normal variable number of tandem repeat (VNTR) of CEL with 16 repeats (16R) on the other, mimicking the genetic make-up seen in MODY8 patients. This mouse model (MODY8/16R) acts as a unique tool to directly interrogate the dynamic communication between the exocrine and endocrine compartments by phenotyping longitudinally from weaning to age 2 yrs. Preliminary histopathological analyses of the pancreata reveal features of CP in some lobes, including inflammation, fibrosis and fat infiltration, mirroring the disease in humans. Moreover, confocal microscopy showed the presence of zymogen granules containing mutant CEL within beta cells. These data argue that the mutant CEL protein is transferred from acinar cells to beta cells in pathological conditions, with implications of directly impacting beta cell viability. Examination of glucose homeostasis revealed that inducing stress (e.g. a high-fat diet) leads to glucose intolerance in MODY8/16R mice compared to their control littermates. In conclusion, the availability of a MODY8/16R mouse model provides a unique opportunity to carefully characterize the endocrine-exocrine communication in the pancreas in a longitudinal manner that is otherwise not possible in humans. Disclosure K.El jellas: None. S.Kahraman: Employee; Boehringer Ingelheim Pharmaceuticals Inc. M.E.Lowe: Other Relationship; MilliporeSigma, Wolters Kluwer Health. A.Molven: None. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago. Funding National Institutes of Health (U01135095)

Safety of gender affirming treatment in assigned female at birth transgender people and association of androgen and estrogen β receptor polymorphisms with clinical outcomes.

Gender affirming hormone treatment (GAHT) with androgens in assigned female at birth (AFAB) people with Gender Incongruence (GI) can induce and maintain variable phenotypical changes, but individual response may be genetically determined. To clarify the role of AR and ERβ polymorphisms we prospectively evaluated AFAB subjects undergoing virilizing GAHT. Fifty-two AFAB people with confirmed GI were evaluated before (T0) and after 6 (T6) and 12 months (T12) of testosterone enanthate 250 mg i.m. every 28 days. Hormone profile (testosterone, estradiol), biochemical (blood count, glyco-metabolic profile) and clinical parameters (Ferriman-Gallwey score, pelvic organs) were evaluated at each time-point, as well as number of CAG and CA repeats for AR and ERβ, respectively. All subjects have successfully achieved testosterone levels within normal male ranges and improved their degree of virilization, in absence of significant side effects. Hemoglobin, hematocrit and red blood cells were significantly increased after treatment, but within normal ranges. Ultrasound monitoring of pelvic organs showed their significant reduction already after 6 months of GATH, in absence of remarkable abnormalities. Furthermore, a lower number of CAG repeats was associated with a higher Ferriman-Gallwey score post treatment and a higher number of CA repeats was associated with uterine volume reduction. We confirmed safety and efficacy of testosterone treatment on all measured parameters. This preliminary data hints a future role of genetic polymorphisms to tailor GAHT in GI people, but evaluation on a larger cohort is necessary as the reduced sample size could limit data generalization at this stage.