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Difficulties in Mutation Screening of the Plasminogen (PLG) Gene in Patients With Ligneous Conjunctivitis and Severe Hypoplasminogenemia

Katrin Tefs, PhD; Louise Kobelt; Maike Ziegler; Boris Hügle, MD; Volker Schuster, MD
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Copyright 2007 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

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Arch Ophthalmol. 2007;125(9):1303-1303. doi:10.1001/archopht.125.9.1303-a
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Leyva-Castillo et al1 described a Mexican patient with ligneous conjunctivitis. Hemostaseologic studies revealed severe hypoplasminogenemia (type I plasminogen deficiency). Mutation screening of the plasminogen (PLG) gene (chromosome 6q26) suggested a 14–base pair deletion in exon 5 of the PLG gene (deleted sequence, GAACTACTGCAGGA). However, this deletion has already been described before as the result of a methodical error: accidental coamplification of sequences of the plasminogen-related gene B (NCBI accession number AC093616.5) located on chromosome 2.2 3 Furthermore, polymerase chain reaction amplification of PLG gene exons 1, 3, 4, 5, 13, 16, and 17 may lead to “false” distinct nucleotide exchanges owing to coamplified PLG homologous genes.3 Optimizing polymerase chain reaction conditions by, for example, increasing the annealing temperature or changing the primers will probably lead to the disappearance of the alleged deletion and false nucleotide exchanges.3 4 Another method to avoid coamplification of PLG homologous genes is a long polymerase chain reaction amplification strategy as described recently.5 In conclusion, the described amplified sequences are not the PLG gene and are possibly derived from PLG-like genes (PLGL) on chromosome 2, or the PLG gene of the patient has undergone a gene conversion with apolipoprotein(a) (LPA) on chromosome 6 or PLGL on chromosome 2.

AUTHOR INFORMATION

Correspondence: Dr Schuster, Hospital for Children and Adolescents, University of Leipzig, Oststrasse 21-25, 04317 Leipzig, Germany (volker.schuster@medizin.uni-leipzig.de).

Financial Disclosure: None reported.

REFERENCES

Leyva-Castillo  JM, Cavazos-Adame  H, Rojas-Martinez  A.  et al.  Ligneous conjunctivitis in a Mexican patient with a mutation in the plasminogen (PLG) gene. Arch Ophthalmol 2006;124 (10) 1500- 1501
PubMed
Tateno  T, Ichinose  A. Expression of plasminogen-related gene B varies among normal tissues and increases in cancer tissues. FEBS Lett 1999;445 (1) 31- 35
PubMed
Sartori  MT, Saggiorato  G, Pellati  D.  et al.  Difficulties in the mutation analysis of plasminogen gene: a study in two patients with ligneous conjunctivitis. Clin Appl Thromb Hemost 2006;12 (1) 77- 84
PubMed
Tefs  K, Gueorguieva  M, Klammt  J.  et al.  Molecular and clinical spectrum of type I plasminogen deficiency: a series of 50 patients. Blood 2006;108 (9) 3021- 3026
PubMed
Siboni  SM, Spreafico  M, Menegatti  M, Martinelli  I, Peyvandi  F. Molecular characterization of an Italian patient with plasminogen deficiency and ligneous conjunctivitis. Blood Coagul Fibrinolysis 2007;18 (1) 81- 84
PubMed

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Leyva-Castillo  JM, Cavazos-Adame  H, Rojas-Martinez  A.  et al.  Ligneous conjunctivitis in a Mexican patient with a mutation in the plasminogen (PLG) gene. Arch Ophthalmol 2006;124 (10) 1500- 1501
PubMed
Tateno  T, Ichinose  A. Expression of plasminogen-related gene B varies among normal tissues and increases in cancer tissues. FEBS Lett 1999;445 (1) 31- 35
PubMed
Sartori  MT, Saggiorato  G, Pellati  D.  et al.  Difficulties in the mutation analysis of plasminogen gene: a study in two patients with ligneous conjunctivitis. Clin Appl Thromb Hemost 2006;12 (1) 77- 84
PubMed
Tefs  K, Gueorguieva  M, Klammt  J.  et al.  Molecular and clinical spectrum of type I plasminogen deficiency: a series of 50 patients. Blood 2006;108 (9) 3021- 3026
PubMed
Siboni  SM, Spreafico  M, Menegatti  M, Martinelli  I, Peyvandi  F. Molecular characterization of an Italian patient with plasminogen deficiency and ligneous conjunctivitis. Blood Coagul Fibrinolysis 2007;18 (1) 81- 84
PubMed

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