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  1. Article ; Online: Chorioangioma: a single tertiary care center retrospective study.

    Saeed, Bashayer / Tulbah, Asma / Bintalib, Marwah / De Vol, Edward Bentz / Almogbel, Samar / BaAli, Mawadah / Bukhari, Hanifa / Foudaneel, Meshayel / Almutairi, Jawaher / Mahfodh, Maram Bin / Tulbah, Maha / Alnemer, Maha / Kurdi, Wesam

    Journal of perinatal medicine

    2023  Volume 51, Issue 5, Page(s) 664–674

    Abstract: Objectives: Chorioangioma represents a challenge due to the rarity of the condition, paucity of sufficient management guidelines, and controversies regarding the best invasive fetal therapy option; most of the scientific evidence for clinical treatment ... ...

    Abstract Objectives: Chorioangioma represents a challenge due to the rarity of the condition, paucity of sufficient management guidelines, and controversies regarding the best invasive fetal therapy option; most of the scientific evidence for clinical treatment has been limited to case reports. The aim of this retrospective study was to review the natural antenatal history, maternal and fetal complications, and therapeutic modalities used in pregnancies complicated with placental chorioangioma at a single Center.
    Methods: This retrospective study was conducted at King Faisal Specialist Hospital and Research Center (KFSH&RC) in Riyadh, Saudi Arabia. Our study population included all pregnancies with ultrasound features of chorioangioma, or histologically confirmed chorioangiomas, between January 2010 and December 2019. Data were collected from the patients' medical records, including the ultrasound reports and histopathology results. All subjects were kept anonymous; case numbers were used as identifiers. Data collected by the investigators were entered into Excel worksheets in an encrypted format. A MEDLINE database was used to retrieve 32 articles for literature review.
    Results: Over a 10-year period between January 2010 and December 2019, 11 cases of chorioangioma were identified. Ultrasound remains the gold standard for diagnosis and follow-up of the pregnancy. Seven of the 11 cases were detected by ultrasound, allowing proper fetal surveillance and antenatal follow-up. Of the remaining six patients, one underwent radiofrequency ablation, two underwent intrauterine transfusion for fetal anemia due to placenta chorioangioma, one had vascular embolization with an adhesive material, and two were managed conservatively until term with ultrasound surveillance.
    Conclusions: Ultrasound remains the gold standard modality for prenatal diagnosis and follow-up of pregnancies with suspected chorioangiomas. Tumor size and vascularity play a significant role in the development of maternal-fetal complications and the success of fetal interventions. To determine the superior modality of fetal intervention mandates more data and research; nevertheless, Fetoscopic Laser Photocoagulation and embolization with adhesive material seem to be a lead choice, with reasonable fetal survival.
    MeSH term(s) Pregnancy ; Humans ; Female ; Retrospective Studies ; Tertiary Care Centers ; Placenta ; Placenta Diseases/diagnosis ; Placenta Diseases/epidemiology ; Placenta Diseases/therapy ; Hemangioma/diagnosis ; Hemangioma/epidemiology ; Hemangioma/therapy ; Ultrasonography, Prenatal
    Language English
    Publishing date 2023-02-23
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 123512-6
    ISSN 1619-3997 ; 0300-5577 ; 0936-174X
    ISSN (online) 1619-3997
    ISSN 0300-5577 ; 0936-174X
    DOI 10.1515/jpm-2021-0085
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Potential health risks of maternal phthalate exposure during the first trimester - The Saudi Early Autism and Environment Study (SEAES).

    Al-Saleh, Iman / Elkhatib, Rola / Alrushud, Nujud / Alnuwaysir, Hissah / Alnemer, Maha / Aldhalaan, Hesham / Shoukri, Mohamed / McWalter, Patricia / Alkhenizan, Abdullah

    Environmental research

    2021  Volume 195, Page(s) 110882

    Abstract: Phthalates are the most ubiquitous contaminants that we are exposed to daily due to their wide use as plasticizers in various consumer products. A few studies have suggested that in utero exposure to phthalates can disturb fetal growth and development in ...

    Abstract Phthalates are the most ubiquitous contaminants that we are exposed to daily due to their wide use as plasticizers in various consumer products. A few studies have suggested that in utero exposure to phthalates can disturb fetal growth and development in humans, because phthalates can interfere with endocrine function. We collected spot urine samples from 291 pregnant women in their first trimester (9.8 ± 2.3 gestational weeks) recruited in an ongoing prospective cohort study in Saudi Arabia. A second urine sample was collected within 1-7 d after enrollment. The aims of this study were to: (1) assess the extent of exposure to phthalates during the first trimester and (2) estimate the risk from single and cumulative exposures to phthalates. Most phthalate metabolites' urinary levels were high, several-fold higher than those reported in relevant studies from other countries. The highest median levels of monoethyl phthalate, mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), and mono-(2-ethylhexyl) phthalate (MEHP) in μg/l (μg/g creatinine) were 245.62 (197.23), 114.26 (99.45), 39.59 (34.02), and 23.51 (19.92), respectively. The MEHP levels were highest among three di (2-ethylhexyl) phthalate (DEHP) metabolites. %MEHP
    MeSH term(s) Autistic Disorder ; Environmental Exposure/analysis ; Environmental Pollutants/toxicity ; Female ; Humans ; Phthalic Acids/toxicity ; Pregnancy ; Pregnancy Trimester, First ; Prospective Studies ; Saudi Arabia/epidemiology
    Chemical Substances Environmental Pollutants ; Phthalic Acids ; phthalic acid (6O7F7IX66E)
    Language English
    Publishing date 2021-02-20
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205699-9
    ISSN 1096-0953 ; 0013-9351
    ISSN (online) 1096-0953
    ISSN 0013-9351
    DOI 10.1016/j.envres.2021.110882
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Potential health risks of maternal phthalate exposure during the first trimester - The Saudi Early Autism and Environment Study (SEAES)

    Al-Saleh, Iman / Elkhatib, Rola / Alrushud, Nujud / Alnuwaysir, Hissah / Alnemer, Maha / Aldhalaan, Hesham / Shoukri, Mohamed / McWalter, Patricia / Alkhenizan, Abdullah

    Environmental research. 2021 Apr., v. 195

    2021  

    Abstract: Phthalates are the most ubiquitous contaminants that we are exposed to daily due to their wide use as plasticizers in various consumer products. A few studies have suggested that in utero exposure to phthalates can disturb fetal growth and development in ...

    Abstract Phthalates are the most ubiquitous contaminants that we are exposed to daily due to their wide use as plasticizers in various consumer products. A few studies have suggested that in utero exposure to phthalates can disturb fetal growth and development in humans, because phthalates can interfere with endocrine function. We collected spot urine samples from 291 pregnant women in their first trimester (9.8 ± 2.3 gestational weeks) recruited in an ongoing prospective cohort study in Saudi Arabia. A second urine sample was collected within 1–7 d after enrollment. The aims of this study were to: (1) assess the extent of exposure to phthalates during the first trimester and (2) estimate the risk from single and cumulative exposures to phthalates. Most phthalate metabolites' urinary levels were high, several-fold higher than those reported in relevant studies from other countries. The highest median levels of monoethyl phthalate, mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), and mono-(2-ethylhexyl) phthalate (MEHP) in μg/l (μg/g creatinine) were 245.62 (197.23), 114.26 (99.45), 39.59 (34.02), and 23.51 (19.92), respectively. The MEHP levels were highest among three di (2-ethylhexyl) phthalate (DEHP) metabolites. %MEHP₄, the ratio of MEHP to four di (2-ethylhexyl) phthalate metabolites (∑₄DEHP), was 44%, indicating interindividual differences in metabolism and excretion. The hazard quotient (HQ) of individual phthalates estimated based on the reference dose (RfD) of the U.S. Environmental Protection Agency indicated that 58% (volume-based) and 37% (creatinine-based) of the women were at risk of exposure to ∑₄DEHP (HQ > 1). Based on the tolerable daily intake (TDI) from the European Food Safety Authority, 35/12% (volume-/creatinine-based data) of the women were at risk of exposure to two dibutyl phthalate (∑DBP) metabolites (MiBP and MnBP). The cumulative risk was assessed using the hazard index (HI), the sum of HQs of all phthalates. The percentages of women (volume-/creatinine-based data) at health risks with an HI > 1 were 64/40% and 42/22% based on RfD and TDI, respectively. In view of these indices for assessing risk, our results for the anti-androgenic effects of exposing pregnant women to ∑₄DEHP and ∑DBP early during pregnancy are alarming.
    Keywords United States Environmental Protection Agency ; acceptable daily intake ; autism ; cohort studies ; creatinine ; cumulative risk ; dibutyl phthalate ; excretion ; fetal development ; food safety ; growth and development ; hormone antagonists ; maternal exposure ; metabolism ; metabolites ; pregnancy ; research ; risk assessment ; urine ; Saudi Arabia
    Language English
    Dates of publication 2021-04
    Publishing place Elsevier Inc.
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 205699-9
    ISSN 1096-0953 ; 0013-9351
    ISSN (online) 1096-0953
    ISSN 0013-9351
    DOI 10.1016/j.envres.2021.110882
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Observational cohort study of perinatal outcomes of women with COVID-19.

    Al-Hajjar, Sami / Ibrahim, Lina / Kurdi, Wesam / Tulbah, Maha / Alnemer, Maha / Bin Jabr, Mohammed / Elsaidawi, Weam / Binmanee, Abdulaziz / Ali, Mohanned / Bukhari, Hanifa / Altuwaijri, Leena / Allaboon, Raneem / Alghamdi, Reem / Saeed, Bashayer / Adi, Yasser / Alhamlan, Fatima

    Journal of infection and public health

    2022  Volume 15, Issue 12, Page(s) 1503–1507

    Abstract: Background: Understanding the impact of SARS-CoV-2 infection on pregnancy outcomes and of pregnancy on COVID-19 outcomes is critical for ensuring proper prenatal and antenatal care. No similar studies have been published in Saudi Arabia.: Methods: We ...

    Abstract Background: Understanding the impact of SARS-CoV-2 infection on pregnancy outcomes and of pregnancy on COVID-19 outcomes is critical for ensuring proper prenatal and antenatal care. No similar studies have been published in Saudi Arabia.
    Methods: We performed a prospective cohort study of pregnant women with confirmed SARS-CoV-2 infection who presented at King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Kingdom of Saudi Arabia. COVID-19 staging was performed, pregnancy-related complications were assessed, and neonatal infection was evaluated.
    Results: We enrolled 81 patients (mean age 31.75 years, SD 5.25) of which there were 17 cases in the first trimester, 20 in the second trimester, and 34 in the third trimester. The distribution of COVID-19 severity was 40 patients with Stage A, 36 with Stage B, 4 with Stage C, and 1 with Stage D. Complications were pregnancy loss in 2 patients (one in each first and second trimester) and 1 fetal death after 20 weeks of pregnancy, 7 patients with fetal growth restriction, and 8 with pre-term delivery.
    Conclusions: We did not observe an unusual frequency of pregnancy-related complications due to SARS-CoV-2 infection in this high-risk obstetric population and there was no evidence of vertical transmission in newborns from women who delivered while positive for the virus.
    MeSH term(s) Infant, Newborn ; Pregnancy ; Female ; Humans ; Adult ; COVID-19/epidemiology ; Prospective Studies ; SARS-CoV-2 ; Cohort Studies ; Abortion, Spontaneous
    Language English
    Publishing date 2022-11-11
    Publishing country England
    Document type Observational Study ; Journal Article
    ZDB-ID 2467587-8
    ISSN 1876-035X ; 1876-0341
    ISSN (online) 1876-035X
    ISSN 1876-0341
    DOI 10.1016/j.jiph.2022.11.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder.

    Shankar, Suma P / Grimsrud, Kristin / Lanoue, Louise / Egense, Alena / Willis, Brandon / Hörberg, Johanna / AlAbdi, Lama / Mayer, Klaus / Ütkür, Koray / Monaghan, Kristin G / Krier, Joel / Stoler, Joan / Alnemer, Maha / Shankar, Prabhu R / Schaffrath, Raffael / Alkuraya, Fowzan S / Brinkmann, Ulrich / Eriksson, Leif A / Lloyd, Kent /
    Rauen, Katherine A

    Genetics in medicine : official journal of the American College of Medical Genetics

    2022  Volume 24, Issue 10, Page(s) 2207

    Language English
    Publishing date 2022-10-07
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1455352-1
    ISSN 1530-0366 ; 1098-3600
    ISSN (online) 1530-0366
    ISSN 1098-3600
    DOI 10.1016/j.gim.2022.07.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder.

    Shankar, Suma P / Grimsrud, Kristin / Lanoue, Louise / Egense, Alena / Willis, Brandon / Hörberg, Johanna / AlAbdi, Lama / Mayer, Klaus / Ütkür, Koray / Monaghan, Kristin G / Krier, Joel / Stoler, Joan / Alnemer, Maha / Shankar, Prabhu R / Schaffrath, Raffael / Alkuraya, Fowzan S / Brinkmann, Ulrich / Eriksson, Leif A / Lloyd, Kent /
    Rauen, Katherine A

    Genetics in medicine : official journal of the American College of Medical Genetics

    2022  Volume 24, Issue 7, Page(s) 1567–1582

    Abstract: Purpose: Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs). ...

    Abstract Purpose: Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).
    Methods: Molecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5
    Results: DPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2.
    Conclusion: We provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.
    MeSH term(s) Adenosine Diphosphate/metabolism ; Animals ; Histidine/analogs & derivatives ; Histidine/metabolism ; Humans ; Methyltransferases/genetics ; Mice ; Mice, Inbred C57BL ; Neurodevelopmental Disorders/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Syndrome
    Chemical Substances Saccharomyces cerevisiae Proteins ; Histidine (4QD397987E) ; Adenosine Diphosphate (61D2G4IYVH) ; diphthamide (75645-22-6) ; Methyltransferases (EC 2.1.1.-) ; DPH5 protein, S cerevisiae (EC 2.1.1.98)
    Language English
    Publishing date 2022-04-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1455352-1
    ISSN 1530-0366 ; 1098-3600
    ISSN (online) 1530-0366
    ISSN 1098-3600
    DOI 10.1016/j.gim.2022.03.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Bialleleic PKD1 mutations underlie early-onset autosomal dominant polycystic kidney disease in Saudi Arabian families.

    Al-Hamed, Mohamed H / Alsahan, Nada / Rice, Sarah J / Edwards, Noel / Nooreddeen, Eman / Alotaibi, Maha / Kurdi, Wesam / Alnemer, Maha / Altaleb, Naderah / Ali, Wafa / Al-Numair, Nouf / Almejaish, Najd / Sayer, John A / Imtiaz, Faiqa

    Pediatric nephrology (Berlin, Germany)

    2019  Volume 34, Issue 9, Page(s) 1615–1623

    Abstract: Background: Polycystic kidney disease (PKD) is one of the most common genetic renal diseases and may be inherited in an autosomal dominant or autosomal recessive pattern. Pathogenic variants in two major genes, PKD1 and PKD2, and two rarer genes, GANAB ... ...

    Abstract Background: Polycystic kidney disease (PKD) is one of the most common genetic renal diseases and may be inherited in an autosomal dominant or autosomal recessive pattern. Pathogenic variants in two major genes, PKD1 and PKD2, and two rarer genes, GANAB and DNAJB11, cause autosomal dominant PKD (ADPKD). Early onset and severe PKD can occur with PKD1 and PKD2 pathogenic variants and such phenotypes may be modified by second alleles inherited in trans. Homozygous or compound heterozygous hypomorphic PKD1 variants may also cause a moderate to severe disease PKD phenotype.
    Methods: Targeted renal gene panel followed by Sanger sequencing of PKD1 gene were employed to investigate molecular causes in early onset PKD patients.
    Results: In this study, we report four consanguineous Saudi Arabian families with early onset PKD which were associated with biallelic variants in PKD1 gene.
    Conclusions: Our findings confirm that PKD1 alleles may combine to produce severe paediatric onset PKD mimicking the more severe autosomal recessive ciliopathy syndromes associated with PKD. Screening of parents of such children may also reveal subclinical PKD phenotypes.
    MeSH term(s) Age of Onset ; Child ; Computer Simulation ; Consanguinity ; DNA Mutational Analysis ; Female ; Homozygote ; Humans ; Kidney/diagnostic imaging ; Male ; Mutation ; Polycystic Kidney, Autosomal Dominant/diagnosis ; Polycystic Kidney, Autosomal Dominant/genetics ; Saudi Arabia ; TRPP Cation Channels/genetics ; Ultrasonography
    Chemical Substances TRPP Cation Channels ; polycystic kidney disease 1 protein
    Language English
    Publishing date 2019-05-11
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-019-04267-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Recessive, Deleterious Variants in SMG8 Expand the Role of Nonsense-Mediated Decay in Developmental Disorders in Humans.

    Alzahrani, Fatema / Kuwahara, Hiroyuki / Long, Yongkang / Al-Owain, Mohammed / Tohary, Mohamed / AlSayed, Moeenaldeen / Mahnashi, Mohammed / Fathi, Lana / Alnemer, Maha / Al-Hamed, Mohamed H / Lemire, Gabrielle / Boycott, Kym M / Hashem, Mais / Han, Wenkai / Al-Maawali, Almundher / Al Mahrizi, Feisal / Al-Thihli, Khalid / Gao, Xin / Alkuraya, Fowzan S

    American journal of human genetics

    2020  Volume 107, Issue 6, Page(s) 1178–1185

    Abstract: We have previously described a heart-, eye-, and brain-malformation syndrome caused by homozygous loss-of-function variants in SMG9, which encodes a critical component of the nonsense-mediated decay (NMD) machinery. Here, we describe four consanguineous ... ...

    Abstract We have previously described a heart-, eye-, and brain-malformation syndrome caused by homozygous loss-of-function variants in SMG9, which encodes a critical component of the nonsense-mediated decay (NMD) machinery. Here, we describe four consanguineous families with four different likely deleterious homozygous variants in SMG8, encoding a binding partner of SMG9. The observed phenotype greatly resembles that linked to SMG9 and comprises severe global developmental delay, microcephaly, facial dysmorphism, and variable congenital heart and eye malformations. RNA-seq analysis revealed a general increase in mRNA expression levels with significant overrepresentation of core NMD substrates. We also identified increased phosphorylation of UPF1, a key SMG1-dependent step in NMD, which most likely represents the loss of SMG8--mediated inhibition of SMG1 kinase activity. Our data show that SMG8 and SMG9 deficiency results in overlapping developmental disorders that most likely converge mechanistically on impaired NMD.
    MeSH term(s) Adolescent ; Brain/abnormalities ; Child ; Child, Preschool ; Consanguinity ; Developmental Disabilities/genetics ; Developmental Disabilities/metabolism ; Family Health ; Female ; Gene Deletion ; Genetic Linkage ; Heart Defects, Congenital/genetics ; Homozygote ; Humans ; Infant ; Intracellular Signaling Peptides and Proteins/genetics ; Male ; Nonsense Mediated mRNA Decay ; Pedigree ; Phenotype ; Phosphorylation ; RNA Helicases/metabolism ; RNA, Messenger/metabolism ; RNA-Seq ; Trans-Activators/metabolism ; Young Adult
    Chemical Substances Intracellular Signaling Peptides and Proteins ; RNA, Messenger ; SMG8 protein, human ; Trans-Activators ; RNA Helicases (EC 3.6.4.13) ; UPF1 protein, human (EC 3.6.4.13)
    Language English
    Publishing date 2020-11-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 219384-x
    ISSN 1537-6605 ; 0002-9297
    ISSN (online) 1537-6605
    ISSN 0002-9297
    DOI 10.1016/j.ajhg.2020.11.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel.

    Al-Hamed, Mohamed H / Kurdi, Wesam / Alsahan, Nada / Alabdullah, Zainab / Abudraz, Rania / Tulbah, Maha / Alnemer, Maha / Khan, Rubina / Al-Jurayb, Haya / Alahmed, Ahmed / Tahir, Asma I / Khalil, Dania / Edwards, Noel / Al Abdulaziz, Basma / Binhumaid, Faisal S / Majid, Salma / Faquih, Tariq / El-Kalioby, Mohamed / Abouelhoda, Mohamed /
    Altassan, Nada / Monies, Dorota / Meyer, Brian / Sayer, John A / Albaqumi, Mamdouh

    Journal of medical genetics

    2016  Volume 53, Issue 5, Page(s) 338–347

    Abstract: Background: Inherited cystic kidney disorders are a common cause of end-stage renal disease. Over 50 ciliopathy genes, which encode proteins that influence the structure and function of the primary cilia, are implicated in cystic kidney disease.: ... ...

    Abstract Background: Inherited cystic kidney disorders are a common cause of end-stage renal disease. Over 50 ciliopathy genes, which encode proteins that influence the structure and function of the primary cilia, are implicated in cystic kidney disease.
    Methods: To define the phenotype and genotype of cystic kidney disease in fetuses and neonates, we correlated antenatal ultrasound examination and postnatal renal ultrasound examination with targeted exon sequencing, using a renal gene panel. A cohort of 44 families in whom antenatal renal ultrasound scanning findings in affected cases included bilateral cystic kidney disease, echogenic kidneys or enlarged kidneys was investigated.
    Results: In this cohort, disease phenotypes were severe with 36 cases of stillbirth or perinatal death. Extra renal malformations, including encephalocele, polydactyly and heart malformations, consistent with ciliopathy phenotypes, were frequently detected. Renal gene panel testing identified causative mutations in 21 out of 34 families (62%), where patient and parental DNA was available. In the remaining 10 families, where only parental DNA was available, 7 inferred causative mutations were found. Together, mutations were found in 12 different genes with a total of 13 novel pathogenic variants, including an inferred novel variant in NEK8. Mutations in CC2D2A were the most common cause of an antenatal cystic kidney disease and a suspected ciliopathy in our cohort.
    Conclusions: In families with ciliopathy phenotypes, mutational analysis using a targeted renal gene panel allows a rapid molecular diagnosis and provides important information for patients, parents and their physicians.
    MeSH term(s) Arabs/genetics ; Ciliopathies/genetics ; Ciliopathies/metabolism ; Cytoskeletal Proteins ; DNA Mutational Analysis ; Exons ; Female ; Fetus/metabolism ; Humans ; Infant, Newborn ; Kidney Diseases, Cystic/congenital ; Kidney Diseases, Cystic/genetics ; Kidney Diseases, Cystic/metabolism ; Mutation ; NIMA-Related Kinases/genetics ; Perinatal Death ; Pregnancy ; Proteins/genetics ; Saudi Arabia ; Syndrome
    Chemical Substances CC2D2A protein, human ; Cytoskeletal Proteins ; Proteins ; NEK8 protein, human (EC 2.7.11.1) ; NIMA-Related Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2016-02-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 220881-7
    ISSN 1468-6244 ; 0022-2593
    ISSN (online) 1468-6244
    ISSN 0022-2593
    DOI 10.1136/jmedgenet-2015-103469
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Identification of a novel MKS locus defined by TMEM107 mutation.

    Shaheen, Ranad / Almoisheer, Agaadir / Faqeih, Eissa / Babay, Zainab / Monies, Dorota / Tassan, Nada / Abouelhoda, Mohamed / Kurdi, Wesam / Al Mardawi, Elham / Khalil, Mohamed M I / Seidahmed, Mohammed Zain / Alnemer, Maha / Alsahan, Nada / Sogaty, Samira / Alhashem, Amal / Singh, Ankur / Goyal, Manisha / Kapoor, Seema / Alomar, Rana /
    Ibrahim, Niema / Alkuraya, Fowzan S

    Human molecular genetics

    2015  Volume 24, Issue 18, Page(s) 5211–5218

    Abstract: Meckel-Gruber syndrome (MKS) is a perinatally lethal disorder characterized by the triad of occipital encephalocele, polydactyly and polycystic kidneys. Typical of other disorders related to defective primary cilium (ciliopathies), MKS is genetically ... ...

    Abstract Meckel-Gruber syndrome (MKS) is a perinatally lethal disorder characterized by the triad of occipital encephalocele, polydactyly and polycystic kidneys. Typical of other disorders related to defective primary cilium (ciliopathies), MKS is genetically heterogeneous with mutations in a dozen genes to date known to cause the disease. In an ongoing effort to characterize MKS clinically and genetically, we implemented a gene panel and next-generation sequencing approach to identify the causal mutation in 25 MKS families. Of the three families that did not harbor an identifiable causal mutation by this approach, two mapped to a novel disease locus in which whole-exome sequencing revealed the likely causal mutation as a homozygous splicing variant in TMEM107, which we confirm leads to aberrant splicing and nonsense-mediated decay. TMEM107 had been independently identified in two mouse models as a cilia-related protein and mutant mice display typical ciliopathy phenotypes. Our analysis of patient fibroblasts shows marked ciliogenesis defect with an accompanying perturbation of sonic hedgehog signaling, highly concordant with the cellular phenotype in Tmem107 mutants. This study shows that known MKS loci account for the overwhelming majority of MKS cases but additional loci exist including MKS13 caused by TMEM107 mutation.
    MeSH term(s) Alleles ; Cilia/genetics ; Cilia/metabolism ; Ciliary Motility Disorders/diagnosis ; Ciliary Motility Disorders/genetics ; Ciliary Motility Disorders/metabolism ; Consanguinity ; DNA Mutational Analysis ; Encephalocele/diagnosis ; Encephalocele/genetics ; Encephalocele/metabolism ; Female ; Genetic Heterogeneity ; Genetic Loci ; Genotype ; Hedgehog Proteins/metabolism ; Humans ; Male ; Membrane Proteins/genetics ; Mutation ; Pedigree ; Polycystic Kidney Diseases/diagnosis ; Polycystic Kidney Diseases/genetics ; Polycystic Kidney Diseases/metabolism ; Signal Transduction
    Chemical Substances Hedgehog Proteins ; Membrane Proteins ; TMEM107 protein, human
    Language English
    Publishing date 2015-09-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108742-0
    ISSN 1460-2083 ; 0964-6906
    ISSN (online) 1460-2083
    ISSN 0964-6906
    DOI 10.1093/hmg/ddv242
    Database MEDical Literature Analysis and Retrieval System OnLINE

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