Summary
Tyrosinemia II is an autosomal-recessively inherited condition caused by deficiency in the liver-specific enzyme tyrosine aminotransferase (TAT; EC 2.6.1.5). We have restudied a patient with typical symptoms of tyrosinemia II who in addition suffers from multiple congenital anomalies including severe mental retardation. Southern blot analysis using a human TAT cDNA probe revealed a complete deletion of both TAT alleles in the patient. Molecular and cytogenetic analysis of the patient and his family showed one deletion to be maternally inherited, extending over at least 27 kb and including the complete TAT structural gene, whereas loss of the second TAT allele results from a small de novo interstitial deletion, del 16 (pter→q22.1::q22.3→qter), in the paternally inherited chromosome 16. Three additional loci previously assigned to 16q22 were studied in our patient: haptoglobin (HP), lecithin: cholesterol acyltransferase (LCAT), and the metallothionein gene cluster MT1, MT2. Of these three markers, only the HP locus was found to be codeleted with the TAT locus on the del(16) chromosome.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Azoulay M, Henry I, Tata F, Weil D, Grzeschik KH, Chavez E, McIntyre N, Williamson R, Humphries SE, Junien C (1985) The structural gene for human lecithin: cholesterol acyl transferase (LCAT) maps to 16q22. Cytogenet Cell Genet 40:573
Baas F, Bikker H, van Ommen GJB, de Vijlder JJM (1984) Unusual scarcity of restriction site polymorphism in the human thyroglobulin gene. A linkage study suggesting autosomal dominance of a defective thyroglobulin allele. Hum Genet 67:301–305
Barton DE, Yang-Feng TL, Francke U (1986) The human tyrosine aminotransferase gene mapped to the long arm of chromosome 16 (region 16q22→q24) by somatic cell hybrid analysis and in situ hybridization. Hum Genet 72:221–224
Bensi G, Raugei G, Klefenz H, Cortese R (1985) Structure and expression of the human haptoglobin locus. EMBO J 4:119–126
Buist NRM, Kennaway NG, Fellman JH (1985) Tyrosinemia type II: hepatic cytosol tyrosine aminotransferase deficiency (the “Richner-Hanhart syndrome”). In: Bickel H, Wachtel U (eds) Inherited diseases of amino acid metabolism. Thieme, Stuttgart New York, pp 203–235
Campbell RA, Buist NRM, Jacinto EY, Koler RD, Hecht F, Jones RT (1967) Supertyrosinemia (tyrosine transaminase deficiency), congenital anomalies and mental retardation. Prog Soc Pediatr Res, 15th Meeting: 80
Chandra T, Stackhouse R, Kidd VJ, Woo SLC (1983) Isolation and sequence characterization of a cDNA clone of human antithrombin III. Proc Natl Acad Sci USA 80:1845–1848
Feinberg AP, Vogelstein B (1983) A technique for radiolabelling DNA restriction endonuclease fragment to high specific activity. Anal Biochem 132:6–13
Fellman JH, Vanbellinghen PJ, Jones RT, Koler RD (1969) Soluble and mitochondrial forms of tyrosine aminotransferase. Relationship to human tyrosinemia. Biochemistry 8:615–622
Francke U, Oliver N (1978) Quantitative analysis of high-resolution trypsin-Giemsa bands on human prometaphase chromosomes. Hum Genet 45:137–165
Goldsmith LA, (1983) Tyrosinemia and related disorders. In: Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 287–299
Harper ME, Saunders GF (1981) Localization of single copy DNA sequences on G-banded human chromosomes by in situ hybridization. Chromosoma 83:431–439
ISCN (1985) An international system for human cytogenetic nomenclature. Birth Defects, Original Article Ser 21, no 1, March of Dimes Birth Defects Foundation
Jarman AP, Nicholls RD, Weatherall DJ, Clegg JB, Higgs DR (1986) Molecular characterization of a hypervariable region downstream of the human α-globin gene cluster. EMBO J 5:1857–1863
Karin M, Eddy RL, Henry WM, Haley LL, Byers MG, Shows TB (1984) Human metallothionein genes are clustered on chromosome 16. Proc Natl Acad Sci USA 81:5494–5498
Kennaway NG, Buist NRM (1971) Metabolic studies in a patient with hepatic cytosol tyrosine aminotransferase deficiency. Pediatr Res 5:287–297
Lauer J, Shen CKJ, Maniatis T (1980) The chromosomal arrangement of human α-like globin genes: sequence homology and α-globin gene deletion. Cell 20:119–130
Laurell C-B (1966) Quantitative estimation of protein, by electrophoresis in agarose gel containing antibody. Anal Biochem 15:45–52
Le Beau MM, Diaz MO, Karin M, Rowley JD (1985) Metalothionein gene cluster is split by chromosome 16 rearrangements in myelomonocytic leukemia. Nature 313:709–711
Lin CC, Lowry RB, Snyder FF (1983) Interstitial delection for a region in the long arm of chromosome 16. Hum Genet 65:134–138
McGill JR, Yang F, Baldwin WD, Brune JL, Barnett DR, Bowman BH, Moore CM (1984) Localization of the haptoglobin α and β genes (HPA and HPB) to human chromosome 16q22 by in situ hybridization. Cytogenet Cell Genet 38:155–157
Magenis E, Chamberlin J (1979) Location of fragile site: 16q22.00. Cytogenet Cell Genet 25:180–181
Magenis RE, Hecht F, Lovrien EW (1970) Heritable fragile site on chromosome 16: probable localization of haptoglobin locus in man. Sciene 170:85–87
Natt E, Kao FT, Rettenmeier R, Scherer G (1986) Assignment of the human tyrosine aminotransferase gene to chromosome 16. Hum Genet 72:225–228
Oliviero S, De Marchi M, Bensi G, Raugei G, Carbonara AO (1985) A new restriction fragment length polymorphism in the haptoglobin gene region. Hum Genet 70:66–70
Poulik MD (1957) Starch gel electrophoresis in a discontinous system of buffers. Nature 180:1477
Poustka A, Rackwitz HR, Frischauf AM, Hohn B, Lehrach H (1984) Selective isolation of cosmid clones by homologous recomination in Escherichia coli. Proc Natl Acad Sci USA 81:4129–4133
Raugei G, Bensi G, Colantuoni V, Romano V, Santoro C, Costanzo F, Cortese R (1983) Sequence of human haptoglobin cDNA: evidence that the α and β subunits are coded by the same mRNA. Nucleic Acids Res 11:5811–5819
Reed KC, Mann DA (1985) Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res 13:7207–7221
Schweizer D (1980) Simulaneous fluorescent staining of R-bands and specific heterochromatic regions (DA-DAPI bands) in human chromosomes. Cytogenet Cell Genet 27:190–193
Seabright M (1971) A rapid banding technique for human chromosomes. Lancet II: 971–972
Tata F, Chavez E, Markham AF, Scrace GT, Waterfield MD, McIntyre N, Williamson R, Humphries SE (1987) Isolation and characterization of cDNA clones for human LCAT. Biochem Biophys Res Commun (in press)
Teisberg P, Gjone E, Olaisen B (1975) Genetics of LCAT (lecithin: cholesterol acyltransferase) deficiency. Ann Hum Genet 38:327–331
Wigler M, Pellicer A, Silverstein S, Axel R, Urlaub G, Chasin L (1979) DNA-mediated transfer of the adenine phosphoribosysltransferase locus into mammalian cells. Proc Natl Acad Sci USA 76:1373–1376
Yunis JJ (1976) High resolution of human chromosomes. Science 191:1268–1270
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Natt, E., Westphal, EM., Toth-Fejel, S.E. et al. Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1 → q22.3 in a patient with tyrosinemia type II. Hum Genet 77, 352–358 (1987). https://doi.org/10.1007/BF00291426
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00291426