DOCSLIB.ORG

X Inactivation Patterns in Females with Alport's Syndrome: a Means of Selecting Against a Deleterious Gene?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
X Inactivation Patterns in Females with Alport's Syndrome: a Means of Selecting Against a Deleterious Gene? I Med Genet 1992; 29: 663-666 663 SHORT COMMUNICATIONS J Med Genet: first published as 10.1136/jmg.29.9.663 on 1 September 1992. Downloaded from X inactivation patterns in females with Alport's syndrome: a means of selecting against a deleterious gene? David Vetrie, Frances Flinter, Martin Bobrow, Ann Harris Abstract sensitive enzymes which will not cleave The patterns of X chromosome inactiva- methylated DNA. tion in 43 females from families segreg- In order to establish whether skewed ating classic Alport's syndrome (AS) (X inactivation possibly resulting from selection linked hereditary nephritis with deaf- against cells expressing a mutant AS gene has ness) have been analysed. AS carrier any effect on disease severity in Alport's syn- females have a most variable clinical drome we have now investigated X inactiva- course. The aim ofthe study was to estab- tion patterns in a group of 22 families segregat- lish whether there was any correlation ing for AS. These families were selected from between the X inactivation pattern of a 30 that were previously subjected to extensive carrier female and the severity of her linkage analysis3 because one or more female disease. No correlation was found in DNA members was heterozygous for polymor- derived from peripheral blood lympho- phisms in either of the two X linked genes for cytes. However, it remains possible that HPRT or PGK. X inactivation patterns were differential patterns of X inactivation established in both AS carrier and non-carrier may occur in the tissues affected by AS, females by the analysis of methylation patterns namely the basement membrane of the of one of these two genes. kidney, eye, and ear. Forty-four females from 22 AS families (J Med Genet 1992;29:663-6) were studied. Thirty subjects were classified as AS carriers based on clinical and genetic evid- ence. This group included 25 AS carriers with Classical X linked Alport's syndrome (AS)l2 normal renal function and five subjects with which maps to Xq2l-22'' is caused by muta- impaired renal function (IRF). The remaining http://jmg.bmj.com/ tions in the gene encoding the a5 chain of 14 females were clinically normal and did not basement membrane collagen type IV carry a mutant AS gene (table 1). (COL4A5). Female carriers show a wide Details of the HPRT and PGK polymor- spectrum of severity of expression; some show phisms are described elsewhere.'1-4 Briefly, all the characteristic signs of the disease seen in the HPRT probe detects a polymorphism after male patients, namely chronic renal failure, simultaneous cleavage with BamHI and PvuII high tone sensorineural deafness, and specific giving band sizes of 18 and 12 kb. The PGK on October 2, 2021 by guest. Protected copyright. eye defects (lenticonus and macular flecks), probe detects a polymorphism after simultan- others may only be minimally affected, and the eous cleavage with EcoRI, BglI, and BglII majority remain healthy throughout a normal showing polymorphic fragments of 1-7 and life span, the only sign of AS being micro- Paediatric Research 1-3 kb. The methylated polymorphic allele Unit, Division of scopic haematuria.9 (that is not cleaved by HpaII) has been shown Medical and It has been suggested that the variable phe- to be on the active chromosome for the HPRT Molecular Genetics, notype in carrier females might be related to X United Medical and probe1215 and on the inactive chromosome for Dental Schools of inactivation patterns. Selection against cells the PGK probe."3 Guy's and St expressing the mutant AS allele might result in Total genomic DNA was extracted from Thomas's Hospitals, a less severe disease. Alternatively, inactiva- peripheral blood cells as described previously.3 8th floor, Guy's tion of a Tower, London SE1 high proportion ofnormal X chromo- Digests, Southern blotting, and probing for 9RT. somes in the critical tissues could lead to a HPRT and PGK were carried out as described D Vetrie more severe clinical manifestation. in the accompanying paper.'6 F Flinter It is known that at the DNA M Bobrow level the A Harris phenomenon of X inactivation can be assessed in terms of methylation of certain base se- Correspondence to Dr Harris, Paediatric Molecular quences. Polymorphisms in the housekeeping Table 1 X inactivation patterns in AS females and Genetics, Institute of genes hypoxanthine phosphoribosyl transfer- their normal relatives Molecular Medicine, John Radcliffe Hospital, ase (HPRT)'0 and phosphoglycerate kinase AS females Normal relatives Headington, Oxford OX3 (PGK)" have been used to distinguish mater- 9DU. Symmetrical 16 7 nal and paternal X chromosomes. The methy- Moderately skewed 13 6 Received 7 March 1992. lation state of the two polymorphic DNA frag- Extremely skewed 1 1 Revised version accepted Total 30 14 8 May 1992. ments is then investigated using methylation 664 Vetrie, Flinter, Bobrow, Harris X inactivation patterns in subjects were clas- respectively). All four AS females with IRF sified as being symmetrical, moderately who show skewed patterns of X inactivation skewed (that is, an inactivation pattern that have preferentially inactivated the HPRT or deviates noticeably from a 50:50 maternal:pa- PGK locus cosegregating with the mutant J Med Genet: first published as 10.1136/jmg.29.9.663 on 1 September 1992. Downloaded from ternal ratio), or extremely skewed (that is, one allele. Cosegregation of the Alport locus with parental allele being virtually completely in- the HPRT or PGK loci for representative active). Autoradiographs were scanned on a families is illustrated in the figure. The poly- Biorad Model 620 video densitometer and the morphic band sizes are shown for the HPRT symmetrical pattern included subjects with a or PGK markers in the informative family ratio of fragment intensities after HpaII diges- members. The maternal (M) and paternal (P) tion of 50:50 to 65:35, the moderately skewed X chromosomes are shown as having the mu- group included ratios of 65:35 to 80:20, and a tant (AS) or normal (N) COL4A5 allele. In ratio of more than 80:20 was defined as ex- pedigree A, subject 5 has IRF and has prefer- tremely skewed. entially inactivated the X chromosome carry- The X inactivation patterns in Alport's syn- ing both the 12 kb HPRT allele and the mutant drome females and their non-AS relatives are AS gene. Pedigree B shows two subjects (3 and summarised in table 1. Data for HPRT and 4) with IRF who both show moderately PGK have been combined. It is clear that skewed inactivation of the X chromosome about the same proportion of AS (16/30) and bearing the 1 7 kb PGK and mutant AS alleles. non-AS (7/14) women show completely sym- Pedigree C shows subjects without IRF (3 and metrical patterns of X inactivation. Of those 6) who have preferential inactivation of the X showing skewed patterns, 13/14 (93%) of AS chromosome carrying the 17 kb PGK and women and 6/7 (86%) of non-AS females have mutant AS alleles, while pedigree D shows two moderately skewed patterns. The remainder family members without IRF who have sym- show inactivation of the same parental X chro- metrical X inactivation (2) or extremely mosome in all their peripheral blood cells. skewed inactivation (1) of the X chromosome Data relating X inactivation patterns in AS carrying the 17 kb PGK fragment and the females to the severity of their renal disease are normal AS gene. shown in table 2. Subjects with impaired renal In an analysis of 44 females from kindreds function (IRF) are compared with those who segregating for Alport's syndrome we have not merely have microscopic haematuria. In the observed evidence for selection against cells former group, one of five (20%) shows a sym- expressing the mutant Alport's gene as deter- metrical pattern while the remaining four mined by patterns of X inactivation in peri- show a moderately skewed pattern. In the pheral blood cells. The ratios of symmetrical, latter group, 15 of 25 (60%) show a symmetri- moderately skewed, or extremely skewed inac- cal pattern, 9 of 25 (36%) show a moderately tivation patterns among AS females are skewed pattern, and one of 25 (4%) are ex- broadly similar to those seen in their female tremely skewed. relatives without AS (table 1). Furthermore, The X inactivation patterns in AS females they are not substantially different from the have with or without impaired renal function ratios we have observed in a large group of http://jmg.bmj.com/ been further analysed with respect to whether control females, either normal or carrying non- the inactivated HPRT or PGK locus cosegreg- X linked diseases.'6 ates with the Alport lesion. This correlation There does not seem to be any correlation of was possible in 14 families and the data are X inactivation patterns with disease severity in shown in table 3, and illustrated in the figure. AS females (table 2), and since we could only AS females without IRF are seen to inactivate examine five AS females with impaired renal the HPRT or PGK locus cosegregating with function (IRF) the small numbers are likely to the normal allele or the mutant allele at ap- account for the differences between IRF and on October 2, 2021 by guest. Protected copyright. proximately equal frequencies (two and three non-IRF groups (specifically the low percent- age of females with IRF who show symmetri- cal inactivation patterns). This explanation is Table 2 X inactivation patterns in AS carrier females supported by the data in table 3 where X with or without impaired renal function (IRF). inactivation patterns in AS females have been AS without IRF AS with IRF investigated further to determine whether the locus with Symmetrical 15 1 inactive HPRT or PGK segregated Moderately skewed 9 4 the AS mutation or the normal allele.
Load more

Recommended publications
  • The Counsyl Foresight™ Carrier Screen
    The Counsyl Foresight™ Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.counsyl.com | [email protected] | (888) COUNSYL The Counsyl Foresight Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia .................................................................................................................................................................................... 8 21-hydroxylase-deficient Congenital Adrenal Hyperplasia ...........................................................................................................................................................................................10 6-pyruvoyl-tetrahydropterin Synthase Deficiency ..........................................................................................................................................................................................................12 ABCC8-related Hyperinsulinism........................................................................................................................................................................................................................................ 14 Adenosine Deaminase Deficiency .................................................................................................................................................................................................................................... 16 Alpha Thalassemia.............................................................................................................................................................................................................................................................
    [Show full text]
  • Disease Reference Book
    The Counsyl Foresight™ Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.counsyl.com | [email protected] | (888) COUNSYL The Counsyl Foresight Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia .................................................................................................................................................................................... 8 21-hydroxylase-deficient Congenital Adrenal Hyperplasia ...........................................................................................................................................................................................10 6-pyruvoyl-tetrahydropterin Synthase Deficiency ..........................................................................................................................................................................................................12 ABCC8-related Hyperinsulinism........................................................................................................................................................................................................................................ 14 Adenosine Deaminase Deficiency .................................................................................................................................................................................................................................... 16 Alpha Thalassemia.............................................................................................................................................................................................................................................................
    [Show full text]
  • Alport Syndrome of the European Dialysis Population Suffers from AS [26], and Simi- Lar Figures Have Been Found in Other Series
    DOCTOR OF MEDICAL SCIENCE Patients with AS constitute 2.3% (11/476) of the renal transplant population at the Mayo Clinic [24], and 1.3% of 1,000 consecutive kidney transplant patients from Sweden [25]. Approximately 0.56% Alport syndrome of the European dialysis population suffers from AS [26], and simi- lar figures have been found in other series. AS accounts for 18% of Molecular genetic aspects the patients undergoing dialysis or having received a kidney graft in 2003 in French Polynesia [27]. A common founder mutation was in Jens Michael Hertz this area. In Denmark, the percentage of patients with AS among all patients starting treatment for ESRD ranges from 0 to 1.21% (mean: 0.42%) in a twelve year period from 1990 to 2001 (Danish National This review has been accepted as a thesis together with nine previously pub- Registry. Report on Dialysis and Transplantation in Denmark 2001). lished papers by the University of Aarhus, February 5, 2009, and defended on This is probably an underestimate due to the difficulties of establish- May 15, 2009. ing the diagnosis. Department of Clinical Genetics, Aarhus University Hospital, and Faculty of Health Sciences, Aarhus University, Denmark. 1.3 CLINICAL FEATURES OF X-LINKED AS Correspondence: Klinisk Genetisk Afdeling, Århus Sygehus, Århus Univer- 1.3.1 Renal features sitetshospital, Nørrebrogade 44, 8000 Århus C, Denmark. AS in its classic form is a hereditary nephropathy associated with E-mail: [email protected] sensorineural hearing loss and ocular manifestations. The charac- Official opponents: Lisbeth Tranebjærg, Allan Meldgaard Lund, and Torben teristic renal features in AS are persistent microscopic hematuria ap- F.
    [Show full text]
  • Its Place Among Other Genetic Causes of Renal Disease
    J Am Soc Nephrol 13: S126–S129, 2002 Anderson-Fabry Disease: Its Place among Other Genetic Causes of Renal Disease JEAN-PIERRE GRU¨ NFELD,* DOMINIQUE CHAUVEAU,* and MICHELINE LE´ VY† *Service of Nephrology, Hoˆpital Necker, Paris, France; †INSERM U 535, Baˆtiment Gregory Pincus, Kremlin- Biceˆtre, France. In the last two decades, decisive advances have been made in Nephropathic cystinosis, first described in 1903, is an auto- the field of human genetics, including renal genetics. The somal recessive disorder characterized by the intra-lysosomal responsible genes have been mapped and then identified in accumulation of cystine. It is caused by a defect in the transport most monogenic renal disorders by using positional cloning of cystine out of the lysosome, a process mediated by a carrier and/or candidate gene approaches. These approaches have that remained unidentified for several decades. However, an been extremely efficient since the number of identified genetic important management step was devised in 1976, before the diseases has increased exponentially over the last 5 years. The biochemical defect was characterized in 1982. Indeed cysteam- data derived from the Human Genome Project will enable a ine, an aminothiol, reacts with cystine to form cysteine-cys- more rapid identification of the genes involved in the remain- teamine mixed disulfide that can readily exit the cystinotic ing “orphan” inherited renal diseases, provided their pheno- lysosome. This drug, if used early and in high doses, retards the types are well characterized. We have entered the post-gene progression of cystinosis in affected subjects by reducing intra- era. What is/are the function(s) of these genes? What are the lysosomal cystine concentrations.
    [Show full text]
  • Genetic Disorder
    Genetic disorder Single gene disorder Prevalence of some single gene disorders[citation needed] A single gene disorder is the result of a single mutated gene. Disorder Prevalence (approximate) There are estimated to be over 4000 human diseases caused Autosomal dominant by single gene defects. Single gene disorders can be passed Familial hypercholesterolemia 1 in 500 on to subsequent generations in several ways. Genomic Polycystic kidney disease 1 in 1250 imprinting and uniparental disomy, however, may affect Hereditary spherocytosis 1 in 5,000 inheritance patterns. The divisions between recessive [2] Marfan syndrome 1 in 4,000 and dominant types are not "hard and fast" although the [3] Huntington disease 1 in 15,000 divisions between autosomal and X-linked types are (since Autosomal recessive the latter types are distinguished purely based on 1 in 625 the chromosomal location of Sickle cell anemia the gene). For example, (African Americans) achondroplasia is typically 1 in 2,000 considered a dominant Cystic fibrosis disorder, but children with two (Caucasians) genes for achondroplasia have a severe skeletal disorder that 1 in 3,000 Tay-Sachs disease achondroplasics could be (American Jews) viewed as carriers of. Sickle- cell anemia is also considered a Phenylketonuria 1 in 12,000 recessive condition, but heterozygous carriers have Mucopolysaccharidoses 1 in 25,000 increased immunity to malaria in early childhood, which could Glycogen storage diseases 1 in 50,000 be described as a related [citation needed] dominant condition. Galactosemia
    [Show full text]
  • Soonerstart Automatic Qualifying Syndromes and Conditions
    SoonerStart Automatic Qualifying Syndromes and Conditions - Appendix O Abetalipoproteinemia Acanthocytosis (see Abetalipoproteinemia) Accutane, Fetal Effects of (see Fetal Retinoid Syndrome) Acidemia, 2-Oxoglutaric Acidemia, Glutaric I Acidemia, Isovaleric Acidemia, Methylmalonic Acidemia, Propionic Aciduria, 3-Methylglutaconic Type II Aciduria, Argininosuccinic Acoustic-Cervico-Oculo Syndrome (see Cervico-Oculo-Acoustic Syndrome) Acrocephalopolysyndactyly Type II Acrocephalosyndactyly Type I Acrodysostosis Acrofacial Dysostosis, Nager Type Adams-Oliver Syndrome (see Limb and Scalp Defects, Adams-Oliver Type) Adrenoleukodystrophy, Neonatal (see Cerebro-Hepato-Renal Syndrome) Aglossia Congenita (see Hypoglossia-Hypodactylia) Aicardi Syndrome AIDS Infection (see Fetal Acquired Immune Deficiency Syndrome) Alaninuria (see Pyruvate Dehydrogenase Deficiency) Albers-Schonberg Disease (see Osteopetrosis, Malignant Recessive) Albinism, Ocular (includes Autosomal Recessive Type) Albinism, Oculocutaneous, Brown Type (Type IV) Albinism, Oculocutaneous, Tyrosinase Negative (Type IA) Albinism, Oculocutaneous, Tyrosinase Positive (Type II) Albinism, Oculocutaneous, Yellow Mutant (Type IB) Albinism-Black Locks-Deafness Albright Hereditary Osteodystrophy (see Parathyroid Hormone Resistance) Alexander Disease Alopecia - Mental Retardation Alpers Disease Alpha 1,4 - Glucosidase Deficiency (see Glycogenosis, Type IIA) Alpha-L-Fucosidase Deficiency (see Fucosidosis) Alport Syndrome (see Nephritis-Deafness, Hereditary Type) Amaurosis (see Blindness) Amaurosis
    [Show full text]
  • X Inactivation, Female Mosaicism, and Sex Differences in Renal Diseases
    BRIEF REVIEW www.jasn.org X Inactivation, Female Mosaicism, and Sex Differences in Renal Diseases Barbara R. Migeon McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University, Baltimore Maryland ABSTRACT A good deal of sex differences in kidney disease is attributable to sex differences expressed only in the testes, they have to do in the function of genes on the X chromosome. Males are uniquely vulnerable to with testicular function and fertility. With mutations in their single copy of X-linked genes, whereas females are often mosaic, one X chromosome, males have only a sin- having a mixture of cells expressing different sets of X-linked genes. This cellular gle copy of their X-linked genes. mosaicism created by X inactivation in females is most often advantageous, pro- On the other hand, even though fe- tecting carriers of X-linked mutations from the severe clinical manifestations seen males have two copies of these genes, in males. Even subtle differences in expression of many of the 1100 X-linked genes both are not expressed in the same cell. may contribute to sex differences in the clinical expression of renal diseases. Only one X is programmed to work in each diploid somatic cell. All of the other J Am Soc Nephrol 19: 2052–2059, 2008. doi: 10.1681/ASN.2008020198 X chromosomes in the cell become inac- tive during fetal development. Briefly, compensation for X dosage in our spe- Although being female conveys a protec- with normal kidney function. This re- cies is accomplished by a process that en- tive effect on the progression of chronic view addresses the genetic and epigenetic sures only a single X is active in both renal disease, the basis for this sex differ- programs that contribute to the sex dif- sexes.
    [Show full text]
  • Essential Genetics 5
    Essential genetics 5 Disease map on chromosomes 例 Gaucher disease 単一遺伝子病 天使病院 Prader-Willi syndrome 隣接遺伝子症候群，欠失が主因となる疾患 臨床遺伝診療室 外木秀文 Trisomy 13 複数の遺伝子の重複によって起こる疾患 挿画 Koromo 遺伝子の座位あるいは欠失等の範囲を示す Copyright (c) 2010 Social Medical Corporation BOKOI All Rights Reserved. Disease map on chromosome 1 Gaucher disease Chromosome 1q21.1 1p36 deletion syndrome deletion syndrome Adrenoleukodystrophy, neonatal Cardiomyopathy, dilated, 1A Zellweger syndrome Charcot-Marie-Tooth disease Emery-Dreifuss muscular Hypercholesterolemia, familial dystrophy Hutchinson-Gilford progeria Ehlers-Danlos syndrome, type VI Muscular dystrophy, limb-girdle type Congenital disorder of Insensitivity to pain, congenital, glycosylation, type Ic with anhidrosis Diamond-Blackfan anemia 6 Charcot-Marie-Tooth disease Dejerine-Sottas syndrome Marshall syndrome Stickler syndrome, type II Chronic granulomatous disease due to deficiency of NCF-2 Alagille syndrome 2 Copyright (c) 2010 Social Medical Corporation BOKOI All Rights Reserved. Disease map on chromosome 2 Epiphyseal dysplasia, multiple Spondyloepimetaphyseal dysplasia Brachydactyly, type D-E, Noonan syndrome Brachydactyly-syndactyly syndrome Peters anomaly Synpolydactyly, type II and V Parkinson disease, familial Leigh syndrome Seizures, benign familial Multiple pterygium syndrome neonatal-infantile Escobar syndrome Ehlers-Danlos syndrome, Brachydactyly, type A1 type I, III, IV Waardenburg syndrome Rhizomelic chondrodysplasia punctata, type 3 Alport syndrome, autosomal recessive Split-hand/foot malformation Crigler-Najjar
    [Show full text]
  • Genetic Testing Services and Support, from Preconception to Prenatal the Way Many Think About Carrier Screening Is Changing
    Genetic testing services and support, from preconception to prenatal The way many think about carrier screening is changing. Carrier screening, once thought to be a test primarily for specific ethnic groups, is now often recommended for every patient. The American Congress of Obstetricians and Gynecologists (ACOG) recently updated its recommendations, stating that carrier screening for spinal muscular atrophy (SMA), in addition to cystic fibrosis (CF), "should be offered to all women who are considering pregnancy or are currently pregnant."7 COMPREHENSIVE, VERSATILE, COVERING WHAT MATTERS Inheritest® provides carrier screening for more than 110 severe disorders that can cause cognitive or physical impairment and/or require surgical or medical intervention. Selected to focus on severe disorders of childhood onset, and to meet ACOG and the American College of Medical Genetics and Genomics (ACMG) criteria, many of the disorders share a recommendation for early intervention. Inheritest offers multiple panels to suit the diverse needs of your patients: Focuses on mutations for CF, SMA, and fragile X syndrome, with the following carrier risks: CORE PANEL CF: as high as 1 in 248 SMA: as high as 1 in 479 Fragile X syndrome: approximately 3 GENES (varies by ethnicity) (varies by ethnicity) 1 in 259 females (all ethnicities)10 SOCIETY-GUIDED PANEL Includes mutations for more than 13 disorders listed in ACOG and/or ACMG recommendations 14 GENES ASHKENAZI JEWISH Enhanced panel includes mutations for more than 40 disorders relevant to patients of Ashkenazi PANEL 48 GENES Jewish descent COMPREHENSIVE Includes mutations for more than 110 disorders across 144 different genes—includes all disorders in PANEL 144 GENES Core, Society-guided, and Ashkenazi Jewish panels THE CASE FOR EXPANDED CARRIER SCREENING While some providers may only screen for CF or select screening based on ethnicity, the case for more comprehensive screening is becoming clear.
    [Show full text]
  • Inheritest 500 PLUS
    Inheritest® 500 PLUS 525 genes Specimen ID: 00000000010 Container ID: H0651 Control ID: Acct #: LCA-BN Phone: SAMPLE REPORT, F-630049 Patient Details Specimen Details Physician Details DOB: 01/01/1991 Date Collected: 08/05/2019 12:00 (Local) Ordering: Age (yyy/mm/dd): 028/07/04 Date Received: 08/06/2019 Referring: Gender: Female Date Entered: 08/06/2019 ID: Patient ID: 00000000010 Date Reported: 08/21/2019 15:29 (Local) NPI: Ethnicity: Unknown Specimen Type: Blood Lab ID: MNEGA Indication: Carrier screening Genetic Counselor: None SUMMARY: POSITIVE POSITIVE RESULTS DISORDER (GENE) RESULTS INTERPRETATION Spinal muscular atrophy AT RISK AT RISK to be a silent carrier (2+0). For ethnic-specific risk (SMN1) 2 copies of SMN1; positive for revisions see Methods/Limitations. Genetic counseling is NMID: NM_000344 c.*3+80T>G SNP recommended. Risk: AT INCREASED RISK FOR AFFECTED PREGNANCY. See Additional Clinical Information. NEGATIVE RESULTS DISORDER (GENE) RESULTS INTERPRETATION Cystic fibrosis NEGATIVE This result reduces, but does not eliminate the risk to be a (CFTR) carrier. NMID: NM_000492 Risk: NOT at an increased risk for an affected pregnancy. Fragile X syndrome NEGATIVE: Not a carrier of a fragile X expansion. (FMR1) 29 and 36 repeats NMID: NM_002024 Risk: NOT at an increased risk for an affected pregnancy. ALL OTHER DISORDERS NEGATIVE This result reduces, but does not eliminate the risk to be a carrier. Risk: The individual is NOT at an increased risk for having a pregnancy that is affected with one of the disorders covered by this test. For partner's gene-specific risks, visit www.integratedgenetics.com.
    [Show full text]
  • A Model of Autosomal Recessive Alport Syndrome in English Cocker Spaniel Dogs
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 54 (1998), pp. 706–719 A model of autosomal recessive Alport syndrome in English cocker spaniel dogs GEORGE E. LEES,R.GAYMAN HELMAN,CLIFFORD E. KASHTAN,ALFRED F. MICHAEL,LINDA D. HOMCO, NICHOLAS J. MILLICHAMP,YOSHIFUMI NINOMIYA,YOSHIKAZU SADO,ICHIRO NAITO, and YOUNGKI KIM Texas Veterinary Medical Center, Texas A&M University, College Station, Texas, Oklahoma Animal Disease Diagnostic Laboratory, Oklahoma State University, Stillwater, Oklahoma, and Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Department of Molecular Biology and Biochemistry, Okayama University Medical School, Okayama, and Divisions of Immunology and Ultrastructural Biology, Shigei Medical Research Institute, Okayama, Japan A model of autosomal recessive Alport syndrome in English cause progressive glomerular disease [1–3]. In humans with cocker spaniel dogs. Alport syndrome (AS), the nephropathy is frequently asso- Background. Dogs with naturally occurring genetic disorders of basement membrane (type IV) collagen may serve as animal ciated with sensorineural hearing loss and ocular abnormal- models of Alport syndrome. ities. Distinctive ultrastructural changes in glomerular base- Methods. An autosomal recessive form of progressive heredi- ment membranes (GBM) of affected individuals is a tary nephritis (HN) was studied in 10 affected, 3 obligate carrier, prominent characteristic of these disorders [1–3]. and 4 unaffected English cocker spaniel (ECS) dogs. Clinical, In humans AS usually is X-linked, resulting from muta- pathological, and ultrastructural features of the disease were a characterized. Expression of basement membrane (BM) proteins tions in the COL4A5 gene, which encodes the 5 chain of was examined with an immunohistochemical technique using type IV collagen [1, 4].
    [Show full text]
  • EUROCAT Syndrome Guide
    JRC - Central Registry european surveillance of congenital anomalies EUROCAT Syndrome Guide Definition and Coding of Syndromes Version July 2017 Revised in 2016 by Ingeborg Barisic, approved by the Coding & Classification Committee in 2017: Ester Garne, Diana Wellesley, David Tucker, Jorieke Bergman and Ingeborg Barisic Revised 2008 by Ingeborg Barisic, Helen Dolk and Ester Garne and discussed and approved by the Coding & Classification Committee 2008: Elisa Calzolari, Diana Wellesley, David Tucker, Ingeborg Barisic, Ester Garne The list of syndromes contained in the previous EUROCAT “Guide to the Coding of Eponyms and Syndromes” (Josephine Weatherall, 1979) was revised by Ingeborg Barisic, Helen Dolk, Ester Garne, Claude Stoll and Diana Wellesley at a meeting in London in November 2003. Approved by the members EUROCAT Coding & Classification Committee 2004: Ingeborg Barisic, Elisa Calzolari, Ester Garne, Annukka Ritvanen, Claude Stoll, Diana Wellesley 1 TABLE OF CONTENTS Introduction and Definitions 6 Coding Notes and Explanation of Guide 10 List of conditions to be coded in the syndrome field 13 List of conditions which should not be coded as syndromes 14 Syndromes – monogenic or unknown etiology Aarskog syndrome 18 Acrocephalopolysyndactyly (all types) 19 Alagille syndrome 20 Alport syndrome 21 Angelman syndrome 22 Aniridia-Wilms tumor syndrome, WAGR 23 Apert syndrome 24 Bardet-Biedl syndrome 25 Beckwith-Wiedemann syndrome (EMG syndrome) 26 Blepharophimosis-ptosis syndrome 28 Branchiootorenal syndrome (Melnick-Fraser syndrome) 29 CHARGE
    [Show full text]