Abstract
Ten patients with inverted duplication of 8p (inv dup 8p) were studied with cytogenetic, biochemical and molecular techniques. The duplication for the region 8p12-p22 was always associated with a deletion of the locus D8S7 (mapped in 8p23.1) as demonstrated with the probe pSW50 by both in situ hybridization and Southern blot. Restriction fragment length polymorphisms detected by probes pSW50 (1 case) and by pG2LPL35 (locus LPL) (two cases) were informative as to a maternal origin of the anomaly. The activity of glutathione reductase, whose gene maps in the duplicated region at 8p21.1, was increased in all patients. The recognizable phenotype of inv dup 8p includes neonatal hypotonia, prominent forehead, large mouth with everted lower lip, abnormally shaped large ears, brain malformations and severe mental retardation. Our findings indicate that the chromosome rearrangement is homogeneous at least for the presence of the deletion and support the hypothesis of a common mechanism of origin.
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Alkan M, Wood S, Borer U, Hofmann S, Buhler E (1989) Physical mapping of D8S7 and D8S11 to the band 8p23.1 of the short arm of chromosome 8. Nucleic Acids Res 20:8395
Dill FJ, Schertzer M, Sandercock J, Tischler B, Wood S (1987) Inverted tandem duplication generates a duplication deficiency of chromosome 8p. Clin Genet 32:109–113
Feldman GL, Worsham MJ, Babu VR, Weiss L, Van Dyke DL (1990) Inverted duplication of 8p: an identifiable syndrome? Am J Hum Genet 47 [Suppl 3]: A56
Fryns JP, Kleczkowska A, Dereymaeker AM, Hoefnagels M, Here-mans G, Marien J, Van denBergheH (1985) Partial 8p trisomy due to interstitial duplication: karyotype: 46,XX, inv dup (8) (p21.1.-p22). Clin Genet 28:546–549
George DL, Francke U (1976) Gene dosage effect: regional mapping of human glutathione reductase on chromosome 8. Cytogenet Cell Genet 17:282–286
Gill P, Woodroffe S, Lygo JE, Millican ES (1991) Population genetics of four hypervariable loci. Int J Legal Med 104:221–227
Gorinati M, Caufin D, Minelli A, Memo L, Gaspardo G, Dodero A (1991) Inv dup (8)(p21.1–p22.1): further case report and a new hypothesis on the origin of the chromosome abnormality. Clin Genet 39:55–59
Heinzmann C, Ladias J, Antonarakis S, Kirchgessner T, Schotz M Lusis AJ (1987) RFLP for the human lipoprotein lipase (LPL) gene: HindIII. Nucleic Acids Res 15:6763
Higgs DR, Wainscoat JS, Flint J, Hill AVS, Thein SL, Nicholls RD, Teal H, Ayyub H, Peto TEA, Falusi AG, Jarman AP, Clegg JB, Weatherall DJ (1986) Analysis of the human alpha-globin gene cluster revealed a highly informative locus. Proc Natl Acad Sci USA 83: 5165–5169
Hongell K, Knuutila S, Westermarck T (1978) Two cases of abnormal short arm of chromosome (8p+) associated with mental retardation. Clin Genet 13:237–240
Hu X, Worton RG (1992) Partial gene duplication as a cause of human diseases. Hum Mutat 1:3–12
Jensen PKA, Junien C, Despoisse S, Bernsen A, Thelle T, Friedrich U, Chapelle A de la (1982) Inverted tandem duplication of the short arm of chromosome 8: a non-random de novo structural aberration in man. Localization of the gene for glutathione reductase in subband 8p21.1. Ann Genet 25:207–211
Kleczkowska A, Fryns JP, D'Hondt F, Jaeken J, Van den Berghe H (1987) Partial duplication 8p due to interstitial duplication: invdup(8)(p21.1-p22). Ann Genet (Paris) 30:47–51
Mattei JF, Mattei MG, Ardissone JP, Coignet J, Giraud F (1980) Clinical, enzyme, and cytogenetic investigations in three new cases of trisomy 8p. Hum Genet 53:315–321
Mitchell J, Menard E, Delneste D, Scarpelli H, Luscombe S, Sparkes R, Hayden M, Weber B, Vekemans M, Der Kaloustian V (1991) Molecular and biochemical evidence for an interstitial deletion associated with an inverted tandem duplication of the short arm of chromosome 8 (abstract). Am J Hum Genet 49 [Suppl 4]:286
Monnat Jr RJ, Hackmann AFM, Chiaverotti TA (1992) Nucleotide sequence analysis of human hypoxanthine phosphoribosyltransferase (HPRT) gene deletions. Genomics 13:777–787
Morris T, Thacker J (1993) Formation of large deletions by illegitimate recombination in the HPRT gene of primary human fibroblasts. Proc Natl Acad Sci USA 90:1392–1396
Nakamura Y, Gillilan S, O'Connel P, Leppert M, Lathrop GM, Lalouel JM, White R (1987a) Isolation and mapping of a polymorphic DNA sequence pYNH24 on chormosome 2 (D2S44). Nucleic Acids Res 15:10073
Nakamura Y, Leppert M, O'Connel P, Wolff R, Holm T, Culver M, Martin C, Fujimoto E, Hoff M, Kumkin E, White R (1987b) Variable number of tandem repeat (VNTR) markers for human gene mapping. Science 235:1616–1622
Nevin NC, Morrison PJ, Jones J, MacC Reid M (1990) Inverted tandem duplication of 8p12-p23.1 in a child with increased activity of glutathione reductase. J Med Genet 27:135–136
Raimondi E, Bardoni B, Rinaldi E, Camerino G (1987) A TaqI RFLP detecting a single copy fragment (G80) from chromosome 7 p13-p15 (D7S373). Nucleic Acids Res 15:7653
Rethoré MO, Aurias A, Couturier J, Dutrillaux B, Prieur M, Leje-une J (1977) Chromosome 8: trisomic complète et trisomie segmentaires. Ann Génét (Paris) 20:5–11
Schinzel A (1984) Catalogue of unbalanced chromosome aberrations in man. DeGruyter, Berlin New York, pp 325–328
Sparkes RS, Zollman S, Klisak I, Kirchgessner TG, Komaromy MC, Mohandas T, Schotz MC, Lusis AJ (1987) Human genes involved in lipolysis of plasma lipoproteins: mapping of loci for lipoprotein lipase to 8p22 and hepatic lipase to 15q21. Genomics 1:138–144
Steinbrueck T, Read C, Daiger SP, Sadler LA, Weber JL, Wood S, Donis-Keller H (1992) A comprehensive genetic linkage map of the human genome. Chromosome 8. Science 258:67–71
Taylor KM, Francke U, Brown MG, George DL, Kaufhold M (1977) Inverted tandem (“mirror”) duplications in human chromosomes: inv dup 8p, 4q 22q. Am J Med Genet 1:3–19
Weleber RG, Verma RS, Kimberling WJ, Fieger HG, Lubs HA (1976) Duplication deficiency of the short arm of chromosome 8 following artificial insemination. Ann Génét (Paris) 19:241–247
Wood S, Poon R, Riddell DC, Royle NJ, Hamerton JL (1986a) A DNA marker for human chromosome 8 that detects alleles of differing sizes. Cytogenet Cell Genet 42:113–118
Wood S, Starr TV, Shukin RJ (1986b) Isolation and characterization of DNA probes from a flow-sorted human chromosome 8 library that detect restriction fragment length polymorphism. Am J Hum Genet 39:744–750
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Minelli, A., Floridia, G., Rossi, E. et al. D8S7 is consistently deleted in inverted duplications of the short arm of chromosome 8 (inv dup 8p). Hum Genet 92, 391–396 (1993). https://doi.org/10.1007/BF01247342
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DOI: https://doi.org/10.1007/BF01247342