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PRENATAL TRISOMY 20 MOSAICISM: ORIGIN IN FETAL KIDNEY CELLS?
1111 As others have noted (see Mascarello et alll) trisomic cell lines be verified in most cases of prenatally diagnosed trisomy 20 mosaicism after termination of pregnancy. However, kidney tissue was not examined in these cases. McDermott et al.13 reported on trisomic cell lines in skin and placental membranes of a phenotypically normal fetus while fetal lung cultures were normal. M. Mikkelsen (unpublished) has detected a trisomic cell line in rectal tissue, and Boue et al.8 noted such a cell line in renal tissue
requiring systemic corticosteroids besides increased inhaler doses. She was again shown to be toxic (T4 179 nmol/l, T3 6 - 5 nmol/1) and was given a second dose of radioiodine (2mCi). She eventually became euthyroid when her PEFR had risen to 2701/min. This is the fourth report of patients with asthma becoming worse with the development ofthyrotoxicosisl-3 and this may represent the mechanism for the TRH induced bronchospasm described by McFadden et al. rather than a direct effect of TRH itself. The mechanism of thyroid hormone induced wheeze is by no means clear. In normal subjects rendered hyperthyroid with T3, airway reactivity remained unaffected,which might be expected in view of5 the increased (3-adrenergic responsiveness seen in thyrotoxicosis. In vitro studies by Hoult et al.have shown that rats made hyperthyroid with T4 have reduced pulmonary breakdown ofPGE2 and PGF2,,. This suggests that wheeze induced by thyroid stimulation may be mediated by prostaglandins. Department of Respiratory Medicine, Guy’s Hospital,
JON AYRES T. J. H. CLARK
London SE1 9RT
cannot
only. These findings show that trisomy 20 mosaicism in amniotic fluid cells is not necessarily due to in vitro non-dysjunction, but may well originate from fetal cells in vivo. However, renal cells were always involved in trisomy 20 mosaicism in those cases where renal tissue had been investigated. The over-representation of trisomy 20 cells in the amniotic fluid culture as compared to the renal tissue culture could indicate that a high percentage of vital cells in the amniotic fluid derive from the
urinary tract. most fetuses with trisomy 20 mosaicism do not display developmental disturbances, termination of pregnancy is not always recommended. In view of the possible renal origin of the trisomic cell line intensive follow-up of kidney development during infancy is recommended.
Since
severe
PRENATAL TRISOMY 20 MOSAICISM: ORIGIN IN FETAL KIDNEY CELLS?
SIR,-The problem of trisomy 20 mosaicism in amniotic fluid cells has been discussed by several workers.7-14 The origin of the trisomic cells is not known exactly, and prognosis and interpretation in prenatal diagnosis are doubtful, making genetic counselling
Institutes for Human Genetics and for Pathology Medizinische Hochschule Lübeck, D-2400 Lübeck, West Germany
difficult. In two cases where prenatal diagnosis was done because of advanced maternal age we found, after in situ amniotic cell culture, a clone-dependent mosaicism 46,XY/47,XY + 20 in different flasks of each case. The parents decided on termination of pregnancy. In one case the detailed pathological examination revealed minor urinary tract anomalies (megapelvis of both kidneys and kinky ureters) in an otherwise anatomically normal fetus, while in the other case a slight facial dysmorphia with micrognathia and retrognathia was found. The urinary tract, however, was normal. Tissue cultures for chromosome analysis were set up from chorion, amnion, skin, pericard, kidney, renal pelvis, upper, middle, and lower ureter, urinary bladder, and urethra. 50 cells per tissue and fetus were analysed. Tissue samples from two control fetuses were also examined. Normal karyotypes were found in all cultures except in samples from kidneys of the two cases with trisomy 20 mosaicism. In one case there were 3 trisomic cells, in the other 7 trisomic cells were found in 50 metaphase plates from these
samples. 1.
Kasperlik-Zaluska A. Asthma
states
in the
course
of hyperthyreosis. Gruzlicka 1966;
36: 581-83. 2.
Settipanae GW, Schoenfeld E, Hamolsky MW. Asthma and hyperthyroidism. J Allergy
Clin Immunol 1972; 49: 348-55. RK, Ehrlich EN, Reed CE. Thyroid disease and asthma. J Allergy Clin Immunol 1977; 59: 398-401. 4. Pratter MR, Irwin RS, Hingston DM, et al. Triiodothyronine (T3) induced hyperthyroidism does not affect airway reactivity in normal subjects. Am Rev Resp Dis 1981; 123: (part 2): 101. 5. Barnes PJ. Radioligand binding studies of adrenergic receptors and their clinical relevance. Br Med J 1981; 282: 1207-10. 6. Hoult JRS, Moore P. Thyroid disease, asthma and prostaglandins. Br Med J 1978; i: 366. 7. Rodriquez ML, Luthy D, Hall JG, Norwood TH, Hoehn H. Amniotic fluid cell mosaicism for presumptive trisomy 20. Clin Genet 1978; 13: 164-68. 8. Boué J, Nicholas H, Barichard F, Boué A. Cloning of amniotic cells helps in the interpretation of mosaicism in prenatal diagnosis. Annales Génet 1979; 22: 3-9. 9. Hoehn H, Rodriquez ML, Norwood TH, Maxwell CL. Mosaicism in amniotic fluid cell cultures: classification and significance. Am J Med Genet 1978; 2: 253-66. 10. Nevin NC, Nevin J, Thompson W. Trisomy 20 mosaicism in amniotic fluid cell culture. Clin Genet 1979; 15: 440-43. 11. Mascarello JT, Chadwick DL, Moyers TG. Trisomy 20 mosaicism in amniotic fluid cells. Lancet 1980; i: 1089. 12. Hsu LYF, Kim HJ, Hausknecht R, Hirschhorn K. Prenatal diagnosis of 45,X/46,XY mosaicism with postnatal confirmation in phenotypically normal male infant. Clin Genet 1976; 10: 232-38. 13. McDermott A, Gardner A, Ray B. Trisomy 20 mosaicism in a foetus. Prenatal Diagnosis 1981; 1: 147-51. 14. Watt JL, Couzin DA, Johnston AW, Jandial V, Gray ES. Prenatal detection of Turner’s syndrome in conjunction with trisomy 20 mosaicism (45,X/46,X,+20). J Med Genet 1981; 18:225-41. 3. Bush
E. SCHWINGER H. REHDER
GLIADIN IN BULLOUS PEMPHIGOID
SIR,-Dr Kieffer and Dr Barnetson (Oct. 10, p. 806) describe antigliadin antibodies (AGA) in the serum of patients with bullous pemphigoid. We have found a raised frequency of AGA in dermatitis herpetiformis1,2 and found high titres of circulating AGA, especially those of IgA class, only in patients who had ,
We used an enzyme-linked evidence of enteropathy. immunosorbent assay (ELISA) and a new indirect immunofluorescent technique to detect AGA. There was a good correlation between the two tests. We are now studying the relation between chronic benign mucous membrane pemphigoid (CBMMP) (a blistering disorder affecting the mucous membranes of the mouth and eyes) and dermatitis herpetiformis. Of the eleven patients with CBMMP studied so far only three have had significantly high titres of AGA by ELISA and only 2 of these were positive by immunofluorescence. The AGA were of IgG class. The finding that no patients had AGA ofIgA class implies that gluten sensitive enteropathy is not associated with this disease. There are no data, as yet, on jejunal biopsies in patients with CBMMP to confirm this. We do not feel, however, that the findings of Kieffer and Barnetson should be ignored. Even in those patients with papillary IgA dermatitis herpetiformis who have no evidence of enteropathy on jejunal biopsy the rash responds to a gluten-free diet.3 In this group of patients clinical response to a gluten-free diet is the only objective evidence of gluten sensitivity. Therefore, absence of gluten sensitivity as the cause of enteropathy per se does not exclude the rash in bullous pemphigoid.44 A recent of abnormal permeability of the gut in patients with eczema, most of whom presumably had a morphologically normal small intestine,6 supports the view that gross morphological abnormality of the small intestine is not a prerequisite for antigen
report
1 Swain AF, Unsworth DJ. Anti-gliadin antibodies in dermatitis herpetiformis. J Roy Soc Med 1981; 74: 458-60. DJ, Leonard JN, McMinn RMH, Swain AF, Holborow EJ, Fry L. Antigliadin antibodies and small-intestinal mucosal damage in dermatitis herpetiformis. Br J Dermatol (in press). 3. Reunala T, Blomquist K, Tarpilla S, Halme H, Kangas K. Gluten free diet in dermatitis herpetiformis. Br J Dermatol 1977; 97: 473-80. 4. Marks J, Shuster S. Small-intestinal mucosa in pemphigoid and subcorneal pustular dermatosis. Arch Dermatol 1969; 100: 136-40. 5. Jackson PG, Lessof MH, Baker RWR, Ferrett J, MacDonald DM Intestinal permeability in patients with eczema and food allergy Lancet 1981; i: 1285-87 6. McCalla R, Savilamti E, Perkkio M, Kuitunen P, Backman A. Morphology of the jejunum in children with eczema due to food allergy. Allergy 1980; 35: 563-71. 2. Unsworth
requiring systemic corticosteroids besides increased inhaler doses. She was again shown to be toxic (T4 179 nmol/l, T3 6 - 5 nmol/1) and was given a second dose of radioiodine (2mCi). She eventually became euthyroid when her PEFR had risen to 2701/min. This is the fourth report of patients with asthma becoming worse with the development ofthyrotoxicosisl-3 and this may represent the mechanism for the TRH induced bronchospasm described by McFadden et al. rather than a direct effect of TRH itself. The mechanism of thyroid hormone induced wheeze is by no means clear. In normal subjects rendered hyperthyroid with T3, airway reactivity remained unaffected,which might be expected in view of5 the increased (3-adrenergic responsiveness seen in thyrotoxicosis. In vitro studies by Hoult et al.have shown that rats made hyperthyroid with T4 have reduced pulmonary breakdown ofPGE2 and PGF2,,. This suggests that wheeze induced by thyroid stimulation may be mediated by prostaglandins. Department of Respiratory Medicine, Guy’s Hospital,
JON AYRES T. J. H. CLARK
London SE1 9RT
cannot
only. These findings show that trisomy 20 mosaicism in amniotic fluid cells is not necessarily due to in vitro non-dysjunction, but may well originate from fetal cells in vivo. However, renal cells were always involved in trisomy 20 mosaicism in those cases where renal tissue had been investigated. The over-representation of trisomy 20 cells in the amniotic fluid culture as compared to the renal tissue culture could indicate that a high percentage of vital cells in the amniotic fluid derive from the
urinary tract. most fetuses with trisomy 20 mosaicism do not display developmental disturbances, termination of pregnancy is not always recommended. In view of the possible renal origin of the trisomic cell line intensive follow-up of kidney development during infancy is recommended.
Since
severe
PRENATAL TRISOMY 20 MOSAICISM: ORIGIN IN FETAL KIDNEY CELLS?
SIR,-The problem of trisomy 20 mosaicism in amniotic fluid cells has been discussed by several workers.7-14 The origin of the trisomic cells is not known exactly, and prognosis and interpretation in prenatal diagnosis are doubtful, making genetic counselling
Institutes for Human Genetics and for Pathology Medizinische Hochschule Lübeck, D-2400 Lübeck, West Germany
difficult. In two cases where prenatal diagnosis was done because of advanced maternal age we found, after in situ amniotic cell culture, a clone-dependent mosaicism 46,XY/47,XY + 20 in different flasks of each case. The parents decided on termination of pregnancy. In one case the detailed pathological examination revealed minor urinary tract anomalies (megapelvis of both kidneys and kinky ureters) in an otherwise anatomically normal fetus, while in the other case a slight facial dysmorphia with micrognathia and retrognathia was found. The urinary tract, however, was normal. Tissue cultures for chromosome analysis were set up from chorion, amnion, skin, pericard, kidney, renal pelvis, upper, middle, and lower ureter, urinary bladder, and urethra. 50 cells per tissue and fetus were analysed. Tissue samples from two control fetuses were also examined. Normal karyotypes were found in all cultures except in samples from kidneys of the two cases with trisomy 20 mosaicism. In one case there were 3 trisomic cells, in the other 7 trisomic cells were found in 50 metaphase plates from these
samples. 1.
Kasperlik-Zaluska A. Asthma
states
in the
course
of hyperthyreosis. Gruzlicka 1966;
36: 581-83. 2.
Settipanae GW, Schoenfeld E, Hamolsky MW. Asthma and hyperthyroidism. J Allergy
Clin Immunol 1972; 49: 348-55. RK, Ehrlich EN, Reed CE. Thyroid disease and asthma. J Allergy Clin Immunol 1977; 59: 398-401. 4. Pratter MR, Irwin RS, Hingston DM, et al. Triiodothyronine (T3) induced hyperthyroidism does not affect airway reactivity in normal subjects. Am Rev Resp Dis 1981; 123: (part 2): 101. 5. Barnes PJ. Radioligand binding studies of adrenergic receptors and their clinical relevance. Br Med J 1981; 282: 1207-10. 6. Hoult JRS, Moore P. Thyroid disease, asthma and prostaglandins. Br Med J 1978; i: 366. 7. Rodriquez ML, Luthy D, Hall JG, Norwood TH, Hoehn H. Amniotic fluid cell mosaicism for presumptive trisomy 20. Clin Genet 1978; 13: 164-68. 8. Boué J, Nicholas H, Barichard F, Boué A. Cloning of amniotic cells helps in the interpretation of mosaicism in prenatal diagnosis. Annales Génet 1979; 22: 3-9. 9. Hoehn H, Rodriquez ML, Norwood TH, Maxwell CL. Mosaicism in amniotic fluid cell cultures: classification and significance. Am J Med Genet 1978; 2: 253-66. 10. Nevin NC, Nevin J, Thompson W. Trisomy 20 mosaicism in amniotic fluid cell culture. Clin Genet 1979; 15: 440-43. 11. Mascarello JT, Chadwick DL, Moyers TG. Trisomy 20 mosaicism in amniotic fluid cells. Lancet 1980; i: 1089. 12. Hsu LYF, Kim HJ, Hausknecht R, Hirschhorn K. Prenatal diagnosis of 45,X/46,XY mosaicism with postnatal confirmation in phenotypically normal male infant. Clin Genet 1976; 10: 232-38. 13. McDermott A, Gardner A, Ray B. Trisomy 20 mosaicism in a foetus. Prenatal Diagnosis 1981; 1: 147-51. 14. Watt JL, Couzin DA, Johnston AW, Jandial V, Gray ES. Prenatal detection of Turner’s syndrome in conjunction with trisomy 20 mosaicism (45,X/46,X,+20). J Med Genet 1981; 18:225-41. 3. Bush
E. SCHWINGER H. REHDER
GLIADIN IN BULLOUS PEMPHIGOID
SIR,-Dr Kieffer and Dr Barnetson (Oct. 10, p. 806) describe antigliadin antibodies (AGA) in the serum of patients with bullous pemphigoid. We have found a raised frequency of AGA in dermatitis herpetiformis1,2 and found high titres of circulating AGA, especially those of IgA class, only in patients who had ,
We used an enzyme-linked evidence of enteropathy. immunosorbent assay (ELISA) and a new indirect immunofluorescent technique to detect AGA. There was a good correlation between the two tests. We are now studying the relation between chronic benign mucous membrane pemphigoid (CBMMP) (a blistering disorder affecting the mucous membranes of the mouth and eyes) and dermatitis herpetiformis. Of the eleven patients with CBMMP studied so far only three have had significantly high titres of AGA by ELISA and only 2 of these were positive by immunofluorescence. The AGA were of IgG class. The finding that no patients had AGA ofIgA class implies that gluten sensitive enteropathy is not associated with this disease. There are no data, as yet, on jejunal biopsies in patients with CBMMP to confirm this. We do not feel, however, that the findings of Kieffer and Barnetson should be ignored. Even in those patients with papillary IgA dermatitis herpetiformis who have no evidence of enteropathy on jejunal biopsy the rash responds to a gluten-free diet.3 In this group of patients clinical response to a gluten-free diet is the only objective evidence of gluten sensitivity. Therefore, absence of gluten sensitivity as the cause of enteropathy per se does not exclude the rash in bullous pemphigoid.44 A recent of abnormal permeability of the gut in patients with eczema, most of whom presumably had a morphologically normal small intestine,6 supports the view that gross morphological abnormality of the small intestine is not a prerequisite for antigen
report
1 Swain AF, Unsworth DJ. Anti-gliadin antibodies in dermatitis herpetiformis. J Roy Soc Med 1981; 74: 458-60. DJ, Leonard JN, McMinn RMH, Swain AF, Holborow EJ, Fry L. Antigliadin antibodies and small-intestinal mucosal damage in dermatitis herpetiformis. Br J Dermatol (in press). 3. Reunala T, Blomquist K, Tarpilla S, Halme H, Kangas K. Gluten free diet in dermatitis herpetiformis. Br J Dermatol 1977; 97: 473-80. 4. Marks J, Shuster S. Small-intestinal mucosa in pemphigoid and subcorneal pustular dermatosis. Arch Dermatol 1969; 100: 136-40. 5. Jackson PG, Lessof MH, Baker RWR, Ferrett J, MacDonald DM Intestinal permeability in patients with eczema and food allergy Lancet 1981; i: 1285-87 6. McCalla R, Savilamti E, Perkkio M, Kuitunen P, Backman A. Morphology of the jejunum in children with eczema due to food allergy. Allergy 1980; 35: 563-71. 2. Unsworth