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1.
Eur J Prev Cardiol ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38669446

ABSTRACT

Improved survival rates for patients with a Fontan circulation has allowed more women with this complex cardiac physiology to contemplate pregnancy. However, pregnancy in women with a Fontan circulation is associated with a high risk of adverse maternal and fetal outcomes, high rates of miscarriage and preterm delivery. Factors associated with a successful pregnancy outcome are: younger age, normal body weight, absence of significant functional limitation, no Fontan-related complications, and well-functioning single ventricle physiology. Appropriate care with timely preconception counselling and regular, frequent clinical reviews by a multidisciplinary team based at a tertiary centre, improves the chance of a successful pregnancy. Empowerment of patients with education on their specific congenital cardiac condition and its projected trajectory, helps them make informed choices regarding their health, reproductive choices and assists them to achieve their life goals.

3.
Expert Rev Cardiovasc Ther ; 21(7): 519-529, 2023.
Article in English | MEDLINE | ID: mdl-37294290

ABSTRACT

INTRODUCTION: Due to the improved survival in individuals with congenital heart disease (CHD), considering their reproductive health has become more important. Currently, this topic is still underexplored. AREAS COVERED: We discuss fertility, sexuality, assisted reproductive technology (ART), and contraception in adults with CHD. EXPERT OPINION: Timely counseling regarding fertility, sexuality, pregnancy, and contraception is necessary, preferably during teenage years. Due to a lack of data, whether or not to perform ART in adults with CHD is almost always based on expert opinion and follow-up in an expert center is recommended. Future research is necessary to fill the gaps in knowledge on the risks and frequency of complications of ART in adults with CHD, but also to be able to differentiate the relative risks in the different types of CHD. Only then will we be able to counsel adults with CHD correctly and not unjustly deprive someone of a chance of pregnancy.


Subject(s)
Heart Defects, Congenital , Sexual Health , Pregnancy , Female , Adolescent , Adult , Humans , Reproductive Health , Contraception , Fertility , Reproductive Techniques, Assisted , Heart Defects, Congenital/complications
4.
Heliyon ; 7(6): e07331, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34195433

ABSTRACT

Nitrogen (N), phosphorus (P) and potassium (K) fertiliser application, was able to counteract growth reductions, in cassava cultivated on nutrient poor soils, under one water stress condition. It however remains to be seen, whether N, P and K fertiliser application, would produce similar results, across different water stress conditions. A study was therefore conducted to determine how N, P and K fertiliser application, would influence cassava growth on nutrient poor soils, under various water stress conditions. Effects on new leaf formation and leaf size were also investigated. The study was a 2×3×4 factorial pot experiment, in a randomised complete block design. It included: two cassava varieties, three water stress levels and four fertiliser treatments. The water stress levels kept some plants watered at field capacities of 30% (severe water stress), 60% (mild water stress) and 100% (zero water stress). The fertiliser treatments consisted of a control (no fertiliser), a sole K fertiliser treatment (25 mg K/kg), a moderate N, P and K fertiliser treatment (25 mg N + 5 mg P + 25 mg K/kg) and a high N, P and K fertiliser treatment (50 mg N + 13 mg P + 50 mg K/kg). All data were analysed using the analysis of variance. Cassava growth was assessed by monitoring changes in the dry shoot mass of cassava plants. High and moderate N, P and K fertiliser application, produced cassava plants with higher and similar dry shoot masses, under mild water stress (10.5 g/plant, SE = 0.6 and 9.0 g/plant, SE = 0.6, respectively). High N, P and K fertiliser application, however gave cassava the highest dry shoot mass, under severe water stress (7.9 g/plant, SE = 0.4). Relatively high cassava growth was consistently achieved with high N, P and K fertiliser application, across all water stress conditions.

5.
PLoS One ; 15(2): e0228641, 2020.
Article in English | MEDLINE | ID: mdl-32053630

ABSTRACT

The use of plant tissue analysis as a tool for attaining low cyanogenic glucoside levels in cassava roots, has hardly been investigated. Just as the quality of crops is improved through the use of plant tissue analysis, the same can probably be done to consistently attain the lowest possible cyanogenic glucoside levels in cassava roots. High levels of cyanogenic glucosides in consumed fresh cassava roots or in their products have the potential of causing cyanide intoxication, hence the need to lower them. An experiment was thus conducted to assess the occurrence of meaningful relationships between plant nutritional status and cyanogenic glucoside production in cassava roots. Total hydrogen cyanide (HCN) levels in cassava roots were used to assess cyanogenic glucoside production. Using NPK fertiliser application to induce changes in plant nutritional status, the main objective of the study was investigated using the following sub-objectives; (1) to determine the effects of increased NPK fertiliser application on cassava root HCN levels; (2) and to show the occurrence of relationships between changes in nutrient levels in plant 'indicator tissue' and HCN levels in cassava roots. The study was a field experiment laid out as a split-plot in a randomized complete block design with three replicates. It was repeated in two consecutive years, with soil nutrient deficiencies only being corrected in the second year. The varieties Salanga, Kalinda, Supa and Kiroba were used in the experiment, while the NPK fertiliser treatments included; a control with no fertiliser applied; a moderate NPK treatment (50 kg N + 10 kg P + 50 kg K /ha); and a high NPK treatment (100 kg N + 25 kg P + 100 kg K /ha). A potassium only treatment (50 kg K/ha) was also included, but mainly for comparison. The root HCN levels of Salanga, Kalinda and Kiroba were significantly influenced by NPK fertiliser application in at least one of the two field experiments, while those of Supa remained uninfluenced. Changes in plant nutritional status in response to fertiliser application were thus shown to influence cyanogenic glucoside production. The results of the multiple linear regression analysis for the first field experiment, generally showed that the root HCN levels of some cassava varieties could have been 'reduced' by decreasing concentrations of nitrogen, potassium and magnesium in plants, or by improving plant calcium concentrations along with NPK fertiliser application. However, in the second field experiment (with corrected soil nutrient deficiencies) the regression analysis generally showed that the root HCN levels of some cassava varieties could have been 'reduced' by improving either one or a combination of the nutrients phosphorous, zinc and potassium in plants along with NPK fertiliser application. Although the results obtained in the two experiments had been contradicting due to slight differences in how they were conducted, the study had nonetheless demonstrated the occurrence of meaningful relationships between plant nutritional status and cyanogenic glucoside production; confirming the possible use of plant tissue analysis in predicting fertiliser needs for the consistent attainment of low cyanogenic glucosides in cassava roots.


Subject(s)
Fertilizers , Glucosides/analysis , Hydrogen Cyanide/analysis , Manihot/chemistry , Nitriles/analysis , Plant Roots/chemistry , Agriculture , Crops, Agricultural/chemistry , Cyanides/analysis , Glycosides/analysis , Hydrogen-Ion Concentration , Linear Models , Nitrogen/analysis , Phosphorus/analysis , Potassium/analysis , Soil
6.
BJOG ; 127(7): 839-846, 2020 06.
Article in English | MEDLINE | ID: mdl-31955489

ABSTRACT

OBJECTIVE: To investigate the intrauterine fetal growth pattern and fetoplacental circulation in pregnancies following bariatric surgery. DESIGN: Prospective study. SETTING: Maternity Unit, UK. POPULATION: One hundred and sixty-two pregnant women; 54 with previous bariatric surgery and 108 with no surgery but similar booking body mass index. METHODS: Participants were seen at 11-14, 20-24, 30-33 and 35-37 weeks of gestation and an oral glucose tolerance test (OGTT) was performed at 27-30 weeks. Fetal head and abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW) and fetoplacental Dopplers were measured at three time-points in pregnancy. Birthweight (BW) was recorded. Variables were modelled after adjustment for maternal/pregnancy characteristics. Model estimates are reported as posterior means and quantile-based 90% credible intervals (CrI). MAIN OUTCOME MEASURES: Fetal biometry, fetoplacental Doppler, BW. RESULTS: Compared with the no surgery group, the post-bariatric surgery group had lower EFW during gestation (up to -120 g; [-189 g, -51 g] lighter) at 35-37 weeks, with smaller AC and FL. Similarly, infants of mothers with previous bariatric surgery had lower average BW [-202 g [-330 g, -72 g] lighter). Overall, there was no difference in the fetoplacental Doppler indices between groups but maternal glucose levels at OGTT were positively correlated with third-trimester EFW and BW. CONCLUSIONS: Fetuses of women with previous bariatric surgery are smaller during pregnancy and at birth, compared with those of women without such surgery, and this may be related to the lower maternal glucose levels seen in the former population. The fetoplacental circulation appears not to be altered by maternal weight loss surgery. TWEETABLE ABSTRACT: Offspring of post-bariatric women are smaller during pregnancy and at birth but this is not due to placental insufficiency.


Subject(s)
Bariatric Surgery/adverse effects , Fetal Development , Placental Circulation , Postoperative Complications/physiopathology , Pregnancy Complications/physiopathology , Adult , Biometry , Birth Weight , Female , Fetal Growth Retardation , Fetal Weight , Humans , Infant, Newborn , Infant, Small for Gestational Age , Obesity/physiopathology , Obesity/surgery , Postoperative Complications/etiology , Postoperative Period , Pregnancy , Pregnancy Complications/etiology , Prospective Studies , Ultrasonography, Prenatal
7.
Clin Exp Immunol ; 199(2): 182-200, 2020 02.
Article in English | MEDLINE | ID: mdl-31617583

ABSTRACT

During human pregnancy, regulatory T cell (Treg ) function is enhanced and immune activation is repressed allowing the growth and development of the feto-placental unit. Here, we have investigated whether human labour is associated with a reversal of the pregnancy-induced changes in the maternal immune system. We tested the hypothesis that human labour is associated with a decline in Treg function, specifically their ability to modulate Toll-like receptor (TLR)-induced immune responses. We studied the changes in cell number, activation status and functional behaviour of peripheral blood, myometrial (myoMC) and cord blood mononuclear cells (CBMC) with the onset of labour. We found that Treg function declines and that Treg cellular targets change with labour onset. The changes in Treg function were associated with increased activation of myoMC, assessed by their expression of major histocompatibility complex (MHC) class II molecules and CBMC inflammatory cells. The innate immune system showed increased activation, as shown by altered monocyte and neutrophil cell phenotypes, possibly to be ready to respond to microbial invasion after birth or to contribute to tissue remodelling. Our results highlight changes in the function of the adaptive and innate immune systems that may have important roles in the onset of human labour.


Subject(s)
Labor, Obstetric/immunology , Monocytes/immunology , Neutrophils/immunology , Pregnancy/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Female , Histocompatibility Antigens Class II/immunology , Humans
8.
Data Brief ; 26: 104456, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31667228

ABSTRACT

Soil moisture management and fertilizer micro-dosing on yield and land utilization efficiency of inter-cropping maize-pigeon-pea in sub humid Tanzania [1]. Farmers typically grow pigeon-pea as a mixed cropping system, the advances of these systems have been well studied, for example: increased productivity and rainfall infiltration. Much research has been done on cereal-pigeon pea intercropping on research stations, comparing yields in intercrops with sole maize. However, the role of inorganic fertilizers in sustainably intensifying intercropping systems has not been optimalised in all cases. For example in a recent study "Sustainable Intensification with Cereal-Legume Intercropping in Eastern and Southern Africa" published in Sustainability 2019, 11, 2891; https://doi.org/10.3390/su11102891, also the effect of inorganic fertilizers were studied. But usually these studies did not pay attention on the relation with water supply. Data in this article presents rainfall variability in the season and between seasons, yield of maize (Zea mays cv. TMV1) and pigeon-pea (Cajanus cajan cv. Babati White) under sole crop and intercropping. Yield of maize and pigeon-pea is analyzed under inter-row rainwater harvesting practices and fertilizer application in the field. Sole cropping and intercropping biological and/or economic yield are used to determine land use efficiency through land equivalent ratio. Comparisons between sites and seasons are done using a T-test.

10.
PLoS One ; 14(5): e0216708, 2019.
Article in English | MEDLINE | ID: mdl-31083702

ABSTRACT

Soils in areas affected by konzo (a cassava cyanide intoxication paralytic disorder) are predominantly infertile and probably unable to supply cultivated cassava with the nutrients it needs to achieve optimal growth. Soil nutrient supply in these areas could also be influencing cyanogenic glucoside production in cassava, however there is hardly any knowledge on this. An assessment of soil nutrient levels on crop fields in konzo-affected areas was therefore carried out to determine their adequacy for optimal cassava growth. Konzo-affected Mtwara region of Tanzania, was used as a case study. Whether soil nutrient supply influences cyanogenic glucoside production in cassava cultivated in konzo-affected areas and how it could be doing this, was additionally investigated. To investigate this, correlations between total hydrogen cyanide (HCN) levels (a measure of cyanogenic glucoside content) in cassava roots and various soil nutrient levels on crops fields were carried out. This was followed by an investigation of relationships between cases of cassava cyanide intoxication and soil nutrient levels on crop fields from which the consumed toxic cassava roots had been harvested. Cases of cassava cyanide intoxication were used as a proxy for high cyanogenic glucoside levels in cassava roots. Logistic regression analysis was used in the latter investigation. Other important non-nutrient soil chemical characteristics, like pH and soil organic carbon, were also included in all analysis performed. The results revealed that most soil nutrients known to have reducing effects on cassava cyanogenic glucosides, like potassium (mean = 0.09 cmol/kg, SD = 0.05 cmol/kg), magnesium (mean = 0.26 cmol/kg, SD = 0.14 cmol/kg) and zinc (mean = 1.34 mg/kg, SD = 0.26 mg/kg) were deficient on several crop fields. The results also showed that cyanogenic glucosides in cassava roots could be increased with the increased supply of sulphur in soils in bitter cassava varieties (rs = 0.593, p = 0.032), and with the increased supply of P in soils in all cassava varieties (rs = 0.486, p = 0.026). The risk of cassava cyanide intoxication occurring (and thus high cyanogenic glucoside levels in cassava) was found to be likely increased by cultivating cassava on soils with high pH (X2 = 8.124, p = 0.004) and high iron (X2 = 5.740, p = 0.017). The study managed to establish that cassava grows under conditions of severe nutrient stress and that soil nutrient supply influences cyanogenic glucoside production in cassava cultivated in konzo-affected areas of Mtwara region. Despite the multiple soil nutrient deficiencies on crop fields, low soil fertility was however not the only probable cause of increased cyanogenic glucosides in cassava, as high soil nutrient levels were also found to be potential contributors.


Subject(s)
Glycosides/analysis , Manihot/growth & development , Soil/chemistry , Carbon/analysis , Cyanides/analysis , Glucosides/analysis , Glycosides/metabolism , Hydrogen-Ion Concentration , Manihot/metabolism , Nutrients/metabolism , Plant Roots/chemistry , Potassium/analysis , Tanzania , Thiocyanates/analysis
11.
PLoS One ; 14(4): e0215527, 2019.
Article in English | MEDLINE | ID: mdl-30998724

ABSTRACT

In areas where konzo (a cassava cyanide related paralytic disorder) persists, the agronomic factors causing increased cyanogenic glucoside levels in cassava, during periods without water stress, are hardly known. However, through their assessment of cassava root toxicity, using its bitter taste, farmers may have noticed factors unrelated to water stress that additionally influence the cyanogenic glucoside content of cassava cultivated in these areas. Increased cassava root bitterness is often associated with an increase in cyanogenic glucoside levels, making it a good indicator of changes in root cyanogenic glucoside content. Bitter cassava varieties that are preferentially planted by people living in most konzo-affected areas, are an additional known contributor to high cyanogenic glucosides. It is water stress that further increases the inherent toxicity of the planted bitter cassava varieties. Using konzo-affected Mtwara region in Tanzania as a case study, a household survey was carried out to identify the overlooked agronomic factors that additionally influence cyanogenic glucoside levels in cassava cultivated in konzo-affected areas. A total of 120 farmers were interviewed and they mentioned a number of factors unrelated to water stress, as agronomic factors that influenced cassava root bitterness and hence cyanogenic glucoside production in cassava. The mentioned factors included; certain soil characteristics (14.2%), plant age at harvest (7.5%), poor weeding (0.8%), piecemeal harvesting (0.8%), and branch pruning (0.8%). The revealed factors constitute permanent environmental characteristics and crop management practices commonly used by farmers living in konzo-affected Mtwara region in Tanzania. The revealed factors could be contributing to increased cyanogenic glucoside levels in cassava, during periods without water stress in areas where konzo persists.


Subject(s)
Farmers , Glycosides/metabolism , Manihot/growth & development , Plant Roots/growth & development , Taste , Thiocyanates/metabolism , Humans , Perception , Tanzania
12.
BJOG ; 126(8): 1025-1031, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30811810

ABSTRACT

OBJECTIVE: Pregnancies in women with Loeys-Dietz syndrome (LDS) are rare and are typically documented in case reports only. Early reports suggested high rates of maternal complications during pregnancy and the puerperium, including aortic dissection and uterine rupture, but information on fetal outcomes was very limited. DESIGN: A retrospective cohort study. SETTING: Eight specialist UK centres. SAMPLE: Pregnant women with LDS. METHODS: Data was collated on cardiac, obstetric, and neonatal outcomes. MAIN OUTCOME MEASURES: Maternal and perinatal outcomes in pregnancies complicated by LDS. RESULTS: Twenty pregnancies in 13 women with LDS were identified. There was one miscarriage, one termination of pregnancy, and 18 livebirths. In eight women the diagnosis was known prior to pregnancy but only one woman had preconception counselling. In four women the diagnosis was made during pregnancy through positive genotyping, and the other was diagnosed following delivery. Five women had a family history of aortic dissection. There were no aortic dissections in our cohort during pregnancy or postpartum. Obstetric complications were common, including postpartum haemorrhage (33%) and preterm delivery (50%). In all, 14/18 (78%) of deliveries were by elective caesarean section, at a median gestational age at delivery of 37 weeks. Over half the infants (56%) were admitted to the neonatal unit following delivery. CONCLUSION: Women with LDS require multidisciplinary specialist management throughout pregnancy. Women should be referred for preconception counselling to make informed decisions around pregnancy risk and outcomes. Early elective preterm delivery needs to be balanced against a high infant admission rate to the neonatal unit. TWEETABLE ABSTRACT: Pregnancy outcomes in women with Loeys-Dietz syndrome.


Subject(s)
Loeys-Dietz Syndrome/complications , Pregnancy Complications/etiology , Pregnancy Outcome , Adult , Delivery, Obstetric/methods , Female , Humans , Infant, Newborn , Postpartum Hemorrhage/etiology , Pregnancy , Premature Birth/etiology , Retrospective Studies , Risk Factors , United Kingdom/epidemiology
13.
Article in English | MEDLINE | ID: mdl-30392581

ABSTRACT

Docosahexaenoic acid (DHA) and arachidonic acid (ArA) are essential brain specific fatty acids (BSFA) for mammalian central nervous system development. Human brains have accelerated growth with significant increase in cerebral content of ArA and DHA during the last trimester of pregnancy and first postnatal months. This randomized double blind placebo controlled single centre trial assessed the impact of BSFA supplementation in pregnancy on newborn infants' brain volumes. Eighty six infants born to study mothers had brain magnetic resonance imaging (MRI) scans soon after birth. Total and regional brain volumes were analyzed and related to maternal supplementation group. Males born to the BSFA supplemented mothers had significantly larger total brain volumes, total gray matter, corpus callosum and cortical volumes when compared to the placebo group. This is the first study to show maternal BSFA supplementation enhances newborn infants' brain size and suggests differential sex sensitivity of fetal brains to pregnancy BSFA status.


Subject(s)
Arachidonic Acid/administration & dosage , Brain/diagnostic imaging , Dietary Supplements , Docosahexaenoic Acids/administration & dosage , Magnetic Resonance Imaging , Pregnancy Trimester, Third , Adult , Brain/embryology , Double-Blind Method , Female , Humans , Infant, Newborn , Male , Pregnancy
15.
Dalton Trans ; 46(46): 15996-15999, 2017 Nov 28.
Article in English | MEDLINE | ID: mdl-29106422

ABSTRACT

Electron localisation function (ELF) calculations have been used to provide the first computational location of the cation lone pairs in apatite materials. We show that the orientation of the lone pairs varies depending on the identity and positions of the channel anions. The results represent a new platform for interpreting experimentally observed structure-property relationships in functional apatites. In particular, they have significant implications for ionic conductivity and suggest that structure-property relationships in lone-pair containing apatite-type solid electrolytes are more complex than previously thought.

16.
Eur Heart J ; 38(35): 2683-2690, 2017 Sep 14.
Article in English | MEDLINE | ID: mdl-28934836

ABSTRACT

AIMS: We report the maternal and foetal outcomes at birth and after 6 months in a cohort of pregnant women with hypertrophic cardiomyopathy (HCM). Although most women with HCM tolerate pregnancy well, there is an increased risk of obstetric and cardiovascular complications. METHODS AND RESULTS: All pregnant women with HCM entered into the prospective worldwide Registry of Pregnancy and Cardiac disease (ROPAC) were included in this analysis. The primary endpoint was a major adverse cardiovascular event (MACE), which included death, heart failure (HF), thrombo-embolic event, and arrhythmia. Baseline and outcome data were analysed and compared for patients with MACE vs. without MACE and for patients with obstructive HCM vs. non-obstructive HCM. Sixty pregnant women (mean age 30.4 ± 6.0 years) with HCM (41.7% obstructive) were included. No maternal mortality occurred in this cohort. In 14 (23%) patients at least one MACE occurred: 9 (15.0%) HF and 7 (12%) an arrhythmia (6 ventricular and 1 atrial fibrillation). MACE occurred most commonly during the 3rd trimester and postpartum period. In total, 3 (5.0%) women experienced foetal loss. Women with MACE had a higher rate of emergency Caesarean delivery for cardiac reasons (21.4% vs. 0%, P = 0.01). No significant differences in pregnancy outcome were found between women with obstructive and non-obstructive HCM. NYHA functional class of ≥II and signs of HF before pregnancy, were associated with MACE. CONCLUSION: Although most women with HCM tolerated pregnancy well, cardiovascular complications were not uncommon and predicted by pre-pregnancy status facilitating pre-pregnancy counselling and targeted antenatal care.


Subject(s)
Cardiomyopathy, Hypertrophic/epidemiology , Pregnancy Complications, Cardiovascular/epidemiology , Adult , Cesarean Section/statistics & numerical data , Female , Global Health , Humans , Pregnancy , Pregnancy Outcome/epidemiology , Prospective Studies , Registries
17.
Int J Cardiol ; 240: 374-378, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28377190

ABSTRACT

BACKGROUND: Women with cardiac disease and their infants are at a greater risk of mortality and morbidity during pregnancy. Expert groups recommend preconception counseling (PCC) for all women with cardiac disease so they are made aware of these risks. We have run a specialist maternal cardiac clinic since 1996. The aim of this study was to evaluate the experience of women who have received PCC within an established multidisciplinary tertiary clinic and to establish their views regarding the counseling they received. METHODS: Single centre prospective study using a patient questionnaire was given to women attending a specialist cardiac preconception counseling clinic from November 2015 to August 2016, with analysis of descriptive data and free text comments from the questionnaire responders. RESULTS: 40/65 returned patient questionnaires. Prior to the consultation fewer than half felt well informed regarding how their heart disease could impact upon pregnancy but a similar proportion felt nonetheless that they would be able to have a healthy pregnancy. Women reported two main areas of concerns, their own health (whether they would survive a pregnancy) and the health of their child. 15% of women reported that these concerns had prevented them from pursuing a pregnancy. Women reported high satisfaction rates with the clinic. CONCLUSIONS: There is an increasing demand for PCC services for women with cardiac disease; our study is the first attempt to determine both the acceptability and the impact of PCC from the patient perspective. Patients reported a high level of satisfaction with the service provided.


Subject(s)
Counseling/methods , Heart Diseases/psychology , Heart Diseases/therapy , Preconception Care/methods , Surveys and Questionnaires , Adult , Female , Heart Diseases/complications , Humans , Prenatal Care/methods , Prenatal Care/psychology , Prospective Studies , Tertiary Care Centers , Young Adult
19.
Clin Genet ; 91(5): 756-763, 2017 05.
Article in English | MEDLINE | ID: mdl-27568816

ABSTRACT

Intellectual disability (ID) affects about 3% of the population and has a male gender bias. Of at least 700 genes currently linked to ID, more than 100 have been identified on the X chromosome, including KIAA2022. KIAA2022 is located on Xq13.3 and is expressed in the developing brain. The protein product of KIAA2022, X­linked Intellectual Disability Protein Related to Neurite Extension (XPN), is developmentally regulated and is involved in neuronal migration and cell adhesion. The clinical manifestations of loss­of­function KIAA2022 mutations have been described previously in 15 males, born from unaffected carrier mothers, but few females. Using whole­exome sequencing, we identified a cohort of five unrelated female patients with de novo probably gene damaging variants in KIAA2022 and core phenotypic features of ID, developmental delay, epilepsy refractory to treatment, and impaired language, of similar severity as reported for male counterparts. This study supports KIAA2022 as a novel cause of X­linked dominant ID, and broadens the phenotype for KIAA2022 mutations.


Subject(s)
Epilepsy , Intellectual Disability , Loss of Function Mutation , Nerve Tissue Proteins , Epilepsy/genetics , Exome , Female , Genes, X-Linked , Humans , Intellectual Disability/genetics , Mutation , Nerve Tissue Proteins/genetics , Nervous System Malformations/genetics , Phenotype
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