DOCSLIB.ORG

Smooth Muscle Tumors Associated with X-Linked Alport Syndrome: Carrier Detection in Females

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Smooth Muscle Tumors Associated with X-Linked Alport Syndrome: Carrier Detection in Females View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 48 (1995), pp. 1900—1906 Smooth muscle tumors associated with X-linked Alport syndrome: Carrier detection in females KARIN DAHAN,1 LAURENCE HEIDET, JING ZHOU, G. ME'ITLER, KATHLEEN A. LEPPIG, WILLEM PROESMANS, ALBERT DAVID, BERNARD ROUSSEL, J.G. MONGEAU, J.M.D GOULD, JEAN-PIERRE GRUNFELD, MARIE-CLAIRE GUBLER, and CORINNE ANTIGNAC INSERM U423, Hôpital Necker-Enfants Malades, Paris, France; Department of Nephrology, Brigham and Woman's Hospital, Boston, Massachusetts, USA; Department of Pediatric Children s Hospital of Eastern Ontario, Ottawa, Canada; Division of Medical Genetics, Children Hospital and Medical Center, Seattle, Washington, USA; Department of Pediatrics, University Hospital, Leuven, Belgium; Service de Pediatric, Centre Hospitalier, Nantes, France; Service de Pediatric, American Memorial Hospital, Reims, France; Service de Pediatrie, Hôpital Sainte Justine, Montreal, Canada; Department of Child Health, The Ipswich Hospital, Ipswich, England, United Kingdom; and Département de Nephrologie, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France Smooth muscle tumors associated with X-linked Alport syndrome: cases with congenital cataracts, has also been reported [5—21]. DL Carrier detection in females. X-linked Alport syndrome (AS) associated is due to benign smooth muscle cell proliferation within the with diffuse esophageal leiomyomatosis (DL) has been reported to be due to deletions removing the 5' ends of both the COL4A5 and COL4A6 esophageal wall [22].Othersmooth muscle tumors, involving the genes, encoding the aS and a6 chains of type IV collagen, respectively, tracheobronchial tree and, in females, the genital tract, are whereas a variety of mutations in COL4A5 has been identified in patients frequent in DL-AS patients [7]. Deletions removing both the 5' with AS alone. Here we report three additional DL-AS patients who also ends of the COL4A5 gene and the recently discovered COL4A6 display deletions removing the 5' ends of both COL4A5 and COL4A6 genes. Furthermore, we tracked the mutation in 15 females belonging to gene [201, encoding the novel a6 type IV collagen chain, have six DL-AS families by gene copy number determination. We found that, been identified in eight unrelated patients with DL-AS [18, 20, like AS, DL is transmitted as an X-linked dominant trait but, contrary to 21]. The COL4A5 and COL4A6 genes are located head-to-head AS, DL is fully penetrant and completely expressed in females. These on chromosome X, at Xq22, with an intergenic region spanning results are in agreement with our previous work suggesting that DL could be due to a dominant effect of an abnormal a6(IV) collagen chain. Finally, only 450 base pairs [20, 231. Furthermore, COL4A6 transcripts we have detected a similar deletion of the COL4A5 and COL4A6 genes in have been detected in fetal esophagus, adult kidney [201 and a DL affected female who showed no sign of nephropathy, demonstrating human lens epithelial cells in culture [23]. These data suggested the AS carrier status of this DL patient. These results emphasize the that a null mutation of COL4A6 or both COL4A5 and COL4A6 importance of molecular analysis of female DL patients for geneticcould be responsible for the leiomyomatosis process. However, counseling. three patients with AS but without leiomyomatosis, and bearing deletions in COL4A5 as well as large deletions in COL4A6, have recently been reported [3, 211, raising the question of the pen- etrance of DL in DL-AS patients. Alport syndrome (AS) is a hereditary nephropathy character- ized by progressive hematuric nephritis with ultrastructural In this report, we extended the study of the molecular defect in changes of the glomerular basement membrane (GBM). In theDL-AS to three additional patients and again found in each majority of the families, AS segregates as an X-linked dominantpatient a deletion involving the 5' ends of both the COL4A5 and trait. Mutations in the COL4A5 gene, which encodes the a5 chainCOL4A6 genes. We also tracked the mutation in 15 females of type IV collagen, a normal component of the GBM, have beenbelonging to six families with DL-AS. We found that, like AS, DL reported in several X-linked AS families [1—3]. The penetranceis a dominant X-linked affection, but, contrary to the renal and expressivity of the renal disease is complete in males but notdisease, DL is completely penetrant and fully expressed in fe- in females, in agreement with the predicted effect of randommales. Finally, we studied the genotype of a female patient inactivation of a mutant X-chromosomal gene [4]. The associationpresenting with DL without any symptoms of nephropathy and of AS with diffuse esophageal leiomyomatosis (DL), and in someshowed that this patient also had a defect in the COL4A5 gene, and was thus carrying AS, a finding of major importance for genetic counseling. Present address: Centre de Genetique Médicale, Université Methods Catholique de Louvain, Bruxellcs, Belgium. The first two authors contrib- uted equally to the work. Patients Received for publication April 21, 1995 Blood samples were collected from two unrelated male (EO, and in revised form June 26, 1995 RD) and one female (HL) patients with the DL-AS association, Accepted for publication July 17, 1995 and from a 43-year-old female patient (MC) with DL alone. © 1995 by the International Society of Nephrology DNAs from 15 female family members of six patients with DL-AS, 1900 Dahan et al: Carrier detection in X-linked DL-AS 1901 two described above (RD, HL) and four (HE, TP, BD and JT) ineDNA probes were used: from the 5' end to the 3' end, JZ4, whom deletions involving both COL4A5 and COL4A6 have beenHT14-2, HT14-3 [241, PL31 and PC4b [25] which encode previously reported [21], were also studied in order to determineCOL4A5 exons 1 to 9, 17 to 27, 28 to 32, 35 to 50 and 51, their carrier status. Among these 15 female relatives, sevenrespectively (Fig. 1A). Two probes derived from JZ3 [20] were belonging to four families (JT, BD, RD, and HE) have clinicalused to span the 5'endof COL4A6: a 145 bp BsrI fragment symptoms of esophageal involvement whereas eight are appar-corresponding to exons 3 and 4, named JZ3FR145, and a 133 bp ently unaffected. The clinical data of patients EU [101, HE [161,MspA3 fragment corresponding to exons 1 and 2, named TP [13] and JT [6] and their affected relatives have been previ-JZ3FR133. The genomic probe LA226-EH is an EcoRI-HindIII ously reported. genomic fragment containing the first exon of COL4A6 and 198 The two male patients (RD and EU) have hematuria (discov-bp of the intergenic region [20]. The probes JZ4, JZ3 and ered at 11 and 2 years, respectively), typical glomerular ultrastruc-LA226-EH all hybridize to an 1.4-kb EcoRI fragment and a 2-kb tural features of Alport syndrome and sensorineural hearing loss.PstI fragment containing both COL4A5 and COL4A6 exons 1. The former developed end-stage renal failure at 25. The latter hasThe ribosomal DNA mouse fragment spanning the 18S rRNA normal GFR, but is only 16. The nine DL-AS affected femalesgene (amino acid residues I to 1644), the sequence of which is [two probands (HE, HL) and seven family members] have hema-extremely homologous among the mouse, rat, rabbit and human tuna, and renal biopsies performed in the two probands showed[26], was used as a reference for quantitation of gene copy alternating thick and thin GBM segments. GFR is normal in allnumber. It reveals an 8-kb EcoRI band and two PstI fragments of but one, who reached ESRD at age 32 (family RD, patient 1113).8 and 12 kb. None of them suffers from hearing loss. Conversely, the eight asymptomatic females had normal results on urinary analysis. Scanning densitometiy The tumoral syndrome includes severe esophageal involvement To determine the gene copy number, Southern blots were in all DL-AS patients. The two male patients (EU and RD) havesuccessively hybridized with the probes tested and with the non-X suffered from recurrent vomiting, dysphagia and epigastric painchromosome rDNA probe. Superimposed autoradiograms were since the ages of 5and 12. They underwent surgical treatment atanalyzed by scanning densitometry (Hoefer Scientific Instruments 8 and 16. The nine female patients with DL-AS displayed theGS300). The peak areas corresponding to each hybridization same kind of digestive symptoms and they all underwent subtotalsignal were calculated by electronic integration. The values for esophagectomy between the ages of 2 and 40. Several of them alsonormal control subjects and for patients were estimated through have respiratory symptoms (dyspnea, wheezing, asthma, bronchi-two or three independent determinations. As the two PstI frag- tis), inferring the likely involvement of the tracheobronchial tree.ments detected by the rDNA probe give a signal of the same Three of five adult females have genital leiomyomas with diffuseintensity (data not shown), either of them could be used as a clitoridal and vulvar hypertrophy (kindred BD, patient 111; kin-control. Different ratios have been deduced from these values dred RD, patient 1113; kindred iT, patient 12). One patient[27]. The R ratio was obtained by dividing the intensity of the developed an adenocarcinoma of the pancreas when she was 48.fragments detected by COL4A5 or COL4A6 probes by the The two male patients as well as two females (kindred BD, patientintensity of the fragments detected with the control probe. The Ill; kindred RD, patient 1113) were found to have bilateralP/C ratio was obtained by dividing the ratio (R) of the patient (P) posterior cataracts. On the contrary, there was no clinical evi-by the ratio of the control (C) individual (normal female patient). dence of esophageal, genital or ocular involvement in the eightA P/C ratio around 1 means that the patient has 2 alleles of the unaffected female members of the six families (mean age of 39fragment of the gene detected by the probe used, whereas a P/C years).
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]