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Cytogenetics of Ph1 negative myeloproliferative disorders
ABSTRACTS OF T H E 7th ANNUAL MEETING The facies as seen by the clinical geneticist is characteristic of the mild type of chondrodysplasia punctata. Ten cases of Binder’s Syndrome have been seen in the South Australian Cranio-Facial Unit and all have facies suggestive of chondrodysplasia punctata. In 9 cases it was not possible t o prove this because skeletal X-rays from early life were not available. In the 10th patient, X-rays of the feet were taken during the 1st yr of life, and they showed the pathognomonic changes of chondrodysplasia punctata (mild type). This report illustrates the clinical findings of the 10 cases and the X-ray findings of the latter cases. It is suggested that most cases of Binder’s Syndrome are in fact the mild form of chondrodysplasia punctata. I . Gorlin RJ, Pindborg JJ, Cohen MM. Syndromes of the head and neck. McCraw-Hill & Co, 1976.
PERINATALLY LETHAL OSTEOGENESIS IMPERFECTACLINICAL AND GENETIC FINDINGS WITH REFLECTION ON THE PATHOGENESIS D. 0. SILLENCE,’ K. A. BARLOW,‘ J. BATEMAN,’ AND W. G. GOLE’ ‘Department of Public Health Biology, University of Sydney and lDepartment of Orthopaedic Surgery, Royal Children 3 Hospital, Melbourne Osteogenesis lmperfecta (01) is now recognized to represent a group of heritable disorders of connective tissue with widely varying liability to fractures. In the last few years considerable progress has been made with the clinical delineation of various groups of 0 1 patients. We (D.O.S. and K.A.B.), with the collaboration of colleagues from overseas and Australia, have recently reviewed 48 cases of perinatally lethal osteogenesis imperfecta (01 type 11). We were led to the conclusion that there is clinical heterogeneity in this group. Three sub-groups were defined: A. Infants with radiographically crumpled lone bones and continuously beaded ribs (due to fractures). B. Infants with crumpled long bones but with few or no rib fractures. C. Infants with poorly modelled, usually twisted and elongated long bones and narrow fractured ribs. Both sporadic and familial (autosornal recessively inherited) cases were observed. No instance of autosomal dominant transmission was observed and there was no elevation of mean paternal age. While the segregation ratio allowing for multiple incomplete ascertainment (proband method), was 0.27k0.06, there is no doubt that the vast majority of cases are sporadic. One possible explanation is that a proportion of sporadic cases reflect dominant mutation. Recent biochemical findings (JB and WGC) indicate that perinatally lethal 0 1 cases have severe tissue collagen deficiency, which in most instances studied would seem to correlate with decreased collagen secretion by cultured skin fibroblasts. Furthermore it would seem at present in the few cases studied in depth that only one collagen gene allele is impaired (Barsh & Byers, PNAS, 1981; 78: 5142-5146). This raises the intriguing question whether these result from truly heterozygous mutation or whether these infants are doubly heterozygous but we are unable to detect the nature of the mutation affecting the other allele. Recent developments in collagen molecular biology indicate that the molecular basis for perinatally lethal 0 1 is extremely varied. Reliable prenatal diagnosis appears to be a reality. All instances of perinatally lethal 0 1 (type 11) should now be studied biochemically, particularly through preservation of cultured skin fibroblast lines, to allow definitive prenatal diagnosis in future pregnancies.
NEWBORN SKELETAL DYSPLASIAS-RECENT DEVELOPMENTS D. SILLENCE’ A N D K. KOZLOWSKI~ ‘Bone Dysplasia Clinic and lDepartment of Radiology, Royal Alexandra Hospital f o r Children, Sydney
107
Of the over 80 osteochondrodysplasias listed in the 2nd International Nomenclature of Constitutional Disorders of the Skeleton 1977, approximately 30 always or commonly present in the newborn period. We have undertaken a joint review of newborn skeletal dysplasias examining clinical and radiographic findings on the one hand and chondro-osseous (growth plate) histopathology where available on the other. This review suggests that there are a large number of cases of newborn skeletal dysplasia which do not readily fit into the categories. A number of syndromes have been recently delineated within this unclassifiable group. Hypochondrogenesis is a generally lethal newborn skeletal dysplasia characterized by epiphyseal dysplasia, platyspondyly with features similar to SED congenita and achondrogenesis type I I . All recorded cases have been sporadic but autosomal recessive inheritance cannot be excluded. Atelosteogenesis was first reported as “Giant-cell Chondrodysplasia”. However, giant-cell transformation in chondrodysplastic cartilage is a non-specific finding. The radiological findings are unique, with hypoplasia of humerus (moon-shaped) and hypoplasia of distal ends of the femora. The fibula is usually absent. All cases have been sporadic. The Kniest-like dysplasias are an underdiagnosed group of disorders with similarities to SED Congenita. This group includes dyssegmental dysplasia, the Rolland-Desbuquois syndrome and the WeissenbacherZweymuller syndrome. The latter might represent a newborn presentation of hereditary arthro-ophthalmopathy (Stickler syndrome).
CHROMOSOME BREAKAGE IN ALZHEIMER’S DISEASE A. SMITH,G. DEN DULK,S. WEYRAUCH, R. MURRAY, M . WILLIAMSON AND G. A. BROE Oliver Latham Laboratory, Sydney, Neurology Department, Lidcombe Hospital, Sydney We present cytogenetic findings for 12 patients with Alzheimer’s Disease (AD), mean age 75.4k6.04 yr and 35 normal age and sex matched controls (mean age 74.8 k 4.04 yr). The study was undertaken because of reports of increased fragments and chromosome breakage in individuals with AD. The study was performed blind on coded peripheral blood specimens, and the allocation of A D or control was not known to the cytogenetic staff until the end of the study. Both the AD group and the controls have been very carefully selected and both underwent the same clinical assessment and screening procedures which included C T scanning. Chromosomes were analysed after 72 hr cultures, using deprived medium TC199 which is known to enhance the appearance of fragile sites. A minimum of 50 cells was examined in each case, and any rearrangement found was classified as ctg, csg, ctb, csb and the chromosome in which it occurred was recorded. Analysis of results showed that there was no statistically significant difference between the A D group and the controls for either the total occurrence of breaks, the type of break or the chromosome(s) involved. In both groups the commonest break was at 3p, followed by a “satellited 16”.
CYTOGENETICS OF Ph’ NEGATIVE MYELOPROLIFERATIVE DISORDERS S. SINCHAND P. C . VINCENT Cytogenetics Unit, Medical Research Department, Kanematsu Memorial Institute, Sydney Hospital Between 1972 and 1982 the Cytogenetics Unit of Sydney Hospital received bone marrow and/or peripheral blood from 140 patients, believed to have a myeloproliferative disorder on clinical grounds. The P h ’ chromosome was seen in 63 of the patients, while the remaining 77 patients showed no Ph’ chromosome. Of these, 13 patients had polycythemia (all showing normal karyotypes), 15 had myelofibrosis
108
Pathology (1984), 16, January
I H F H U V A N CiENF'TIC'S SOCI[.TI' 01- 4L'STR.AL.ASI.A
( I 2 normal and 3 abnormal karyotypes). 33 had a myeloproliferative disorder (23 normal and 10 abnormal karyotypes) and 16 patients had il disorder which clinically and hematologically resembled chronic niyeloid leukemia (so-called Ph' negative CSlL). Ten of these patients showed a normal karyotype while in 6 it was abnormal. In 4 of the 6 Ph' negative CML patients with abnormal karyotype the disease was in an accelerated phase when first seen, while the other 2 went into an accelerated phase shortly afterwards. liaryotypic abnormalities in this sanlple both structural and numerical and were confined to C, D and G group chromosomes.
ANTE-NATAL DfAGNOSlS IN FAMILIES WITH 21 HYDROXYLASE DEFICIENCY 51. S . ST'I t k r j . J. B. HOL.IISTO\, G. GKNSIm , G . WILSOS. F. T. CriKr\Ti.\x\F\ \ X i ) R . L. D,\\\hr\S Deppnrrnieni o j Clinical l i t i i i i i ~ t ~ ~ Royal l ~ ~ . ~ Peril1 , ~ ~ . Hospital. H1.A t)ping o t culturcd amniotic. fibroblasts was done on 2 fetuses in related I'amilies who had one or more children with 21-OH deficiency. I h m the propositi, the 'affected' haplotypes were known to be AI. CW3, BWZZ and AlO, CWJ. BW22 in family I and A25, CLV3. BW22 and A3. C - , B M ' 4 i n famity II. H1.A typing of the amniotic cells was either by direct typing using two-colour fluorescence or a microabsorption technique as described by Pollack et al. Amniotic fluid 17-OH progesterone concentration \\a5 estimated by radioimmunoassay by the method of Boyne and Wilson. HLA typins o l t h e fetus in family 1 showed the presence of Al, A2 wsgestinp that the Fctus had one of the affected haplotypes (Al, CW3. BW22). The fetus in family II was found to have one of the affected haplotypes (A3, BW44). The amniotic fluid concentrations were 5 nmoliL (family I) and 4 nmolil. which excluded homozygous 21-hydrosylasedeficiency (normal range 2.3-7.3 nmoliL.). The k1L.A typing on both infants was confirmed post-natally using peripheral blood lymphocytes and standard NIH methods, suggesting that each infant was heterorggous for 21-OH deficiency, assuming no HLA-8. D recombination. Post-natal 17-OH progesterone estimation arid clinical eumination excluded homozygous ?I-OH deficiency.
THE FRAGILE X CHROMOSOME G~~~~~R. SUTHERLAND Department of Histopathology, The
Adelaide Children 3 Hospital
There will be a small working party sponsored by the National of Health held in Washington on 25-26 April, 1983, to discuss many
aspects of the fragile X. The author will have attended this meeting and will present a summary of current findings and research into the clinical. cytogenetic and molecular genetic aspects of the fragile X.
INDIVIDUAL VARIATION AND SPECIFIC COGNITIVE DEFICITS IN THE FRAGILE X SYNDROME THERESA M. THEOBALD AND DAVID A. HAY Lkpartment of Genetics and Human Variation. La Trobe University, Melbourne
While the fragile X is clearly associated with the X-linked mental retardation, two major behavioural questions have received little attention: (i) the extent and causes of individual variation in IQamong fragile X males and the possibility of some fragile X males being within the normal IQrange. (ii) whether there is a depression in general IQ or whether specific abilities are impaired, as would be likely if the disputed X-linkage of some spatial abilities does exist. These questions were examined in a sample of 53 fragile X males, their mothers who are obligate carriers and their sisters. Among noninstitutionalized males, performance IQranged from 100 to 0. while vocabulary scores ranged from 79-33. The result was that, unlike normal males, their verbal IQfar exceeded their performance IQ. Ability was unrelated to the proportion of cells with a fragile site-but correlated with mother's abilities. The males did exceptionally badly on a digit span task and only one male scored on the backward digit task. This deficit is specific to digits, since their performance on a memory for objects task was adequate. A similar pattern and variability emerged for institutionalized males, except that their abilities overall were much poorer. The mothers performed much better than the daughters, supporting the view that women who have children are a selected subset of the fragile X syndrome. Daughters were extremely variable in performance, which may relate to X chromosome inactivation.
ASSOCIATION OF HLA AND SKIN RESPONSE TO HISTAMINE 51. S. SlLI'hF'I, C . \vll-l, 1.. H. SCHVITT, %I. L.\TTI\IOHt.. R. H'.\RLO\\ .\\D R. 1.. U,\#hiw Ueparm?ent of Jtnmunolog~. Royal Perih Hospital U R Depurttiieni ~ of rltiaiotny and Human Biology, Universiry
of
Western .4ustrulici, Perrh
HLA and disease associations in man are not readily explicable in terms of immune response gene5 or molecular mimicry. Howe\er. evidence is accumulating that HLA genes are asrociated with variation in hormone concentrations or effects. Four hundred and twenty random participants in the 1981 Busselton Health survey were skin tested (prick testing) with 10-fold dilutions of histamine from 10 mg.'ml-' to 10-3m g m l - ' . HLA typing was done by the standard NIH method. The mean weal diametcr of subjects with H I A-€37 was greater than for non-U7 (P<0.005) for all histamine concentraticm except I@' mgiml-'. to which only 24 subjects responded. High frequency of positive responses was also seen in subjects with HLAA3. and IONfrequency in subjects with HLA-BIZ. However, the latter 2 association9 uerc shown by three-way contingency table analysis to be secondary to the association with HLA-B7. This exumplc provider further evidence that some HLA disease association9 may be mediated through an effect of HLA on hormone responsiveness. Further. it suggests that the expression of allergic disease is under the influence of multiple genes, since other factors such as total IgE concentration and specific allergen responsiveness are associated with different HLA phenotypes. or in the case of bronchial reactivity, not significantly associated with HLA.
SMALL SUPERNUMERARY CHROMOSOMES IN AMNIOTIC CELL CULTURES (TWO CASES) L. VOULLAIKE, M.SUSMAN ANDG.ALLEN Department of Luboratory Medicine, Queen Victoria Medical Cenlre. Melbourne
Small supernumerary chromosomes have been found in the normal population as well as in persons with congenital abnormalities and mental retardation. Consequently, the presence of small supernumaary chromosomes in amniotic cell cultures presents a problem in providing accurate prenatal diagnosis. This problem is stressed by 2 unrelated cases with small supernumerary chromosomes in amniotic cell cultures. The origin of the supernumerary chromosomes which appeared in all clones was investigated with various banding techniques, including GTG, CBG, NOR-Ag staining and DAPl staining. In one case the chromosome was bisatellited indicating its acrocentric origin. The pregnancy continues. In the second case the small size of the chromosome did not allow the identification of a specific pattern. The pregnancy was terminated, with a phenotypically normal fetus. In both these cases the parental karyotypes are normal. The poster will illustrate the morphology of supernumerary chromosomes and their banding characteristics.
PERINATALLY LETHAL OSTEOGENESIS IMPERFECTACLINICAL AND GENETIC FINDINGS WITH REFLECTION ON THE PATHOGENESIS D. 0. SILLENCE,’ K. A. BARLOW,‘ J. BATEMAN,’ AND W. G. GOLE’ ‘Department of Public Health Biology, University of Sydney and lDepartment of Orthopaedic Surgery, Royal Children 3 Hospital, Melbourne Osteogenesis lmperfecta (01) is now recognized to represent a group of heritable disorders of connective tissue with widely varying liability to fractures. In the last few years considerable progress has been made with the clinical delineation of various groups of 0 1 patients. We (D.O.S. and K.A.B.), with the collaboration of colleagues from overseas and Australia, have recently reviewed 48 cases of perinatally lethal osteogenesis imperfecta (01 type 11). We were led to the conclusion that there is clinical heterogeneity in this group. Three sub-groups were defined: A. Infants with radiographically crumpled lone bones and continuously beaded ribs (due to fractures). B. Infants with crumpled long bones but with few or no rib fractures. C. Infants with poorly modelled, usually twisted and elongated long bones and narrow fractured ribs. Both sporadic and familial (autosornal recessively inherited) cases were observed. No instance of autosomal dominant transmission was observed and there was no elevation of mean paternal age. While the segregation ratio allowing for multiple incomplete ascertainment (proband method), was 0.27k0.06, there is no doubt that the vast majority of cases are sporadic. One possible explanation is that a proportion of sporadic cases reflect dominant mutation. Recent biochemical findings (JB and WGC) indicate that perinatally lethal 0 1 cases have severe tissue collagen deficiency, which in most instances studied would seem to correlate with decreased collagen secretion by cultured skin fibroblasts. Furthermore it would seem at present in the few cases studied in depth that only one collagen gene allele is impaired (Barsh & Byers, PNAS, 1981; 78: 5142-5146). This raises the intriguing question whether these result from truly heterozygous mutation or whether these infants are doubly heterozygous but we are unable to detect the nature of the mutation affecting the other allele. Recent developments in collagen molecular biology indicate that the molecular basis for perinatally lethal 0 1 is extremely varied. Reliable prenatal diagnosis appears to be a reality. All instances of perinatally lethal 0 1 (type 11) should now be studied biochemically, particularly through preservation of cultured skin fibroblast lines, to allow definitive prenatal diagnosis in future pregnancies.
NEWBORN SKELETAL DYSPLASIAS-RECENT DEVELOPMENTS D. SILLENCE’ A N D K. KOZLOWSKI~ ‘Bone Dysplasia Clinic and lDepartment of Radiology, Royal Alexandra Hospital f o r Children, Sydney
107
Of the over 80 osteochondrodysplasias listed in the 2nd International Nomenclature of Constitutional Disorders of the Skeleton 1977, approximately 30 always or commonly present in the newborn period. We have undertaken a joint review of newborn skeletal dysplasias examining clinical and radiographic findings on the one hand and chondro-osseous (growth plate) histopathology where available on the other. This review suggests that there are a large number of cases of newborn skeletal dysplasia which do not readily fit into the categories. A number of syndromes have been recently delineated within this unclassifiable group. Hypochondrogenesis is a generally lethal newborn skeletal dysplasia characterized by epiphyseal dysplasia, platyspondyly with features similar to SED congenita and achondrogenesis type I I . All recorded cases have been sporadic but autosomal recessive inheritance cannot be excluded. Atelosteogenesis was first reported as “Giant-cell Chondrodysplasia”. However, giant-cell transformation in chondrodysplastic cartilage is a non-specific finding. The radiological findings are unique, with hypoplasia of humerus (moon-shaped) and hypoplasia of distal ends of the femora. The fibula is usually absent. All cases have been sporadic. The Kniest-like dysplasias are an underdiagnosed group of disorders with similarities to SED Congenita. This group includes dyssegmental dysplasia, the Rolland-Desbuquois syndrome and the WeissenbacherZweymuller syndrome. The latter might represent a newborn presentation of hereditary arthro-ophthalmopathy (Stickler syndrome).
CHROMOSOME BREAKAGE IN ALZHEIMER’S DISEASE A. SMITH,G. DEN DULK,S. WEYRAUCH, R. MURRAY, M . WILLIAMSON AND G. A. BROE Oliver Latham Laboratory, Sydney, Neurology Department, Lidcombe Hospital, Sydney We present cytogenetic findings for 12 patients with Alzheimer’s Disease (AD), mean age 75.4k6.04 yr and 35 normal age and sex matched controls (mean age 74.8 k 4.04 yr). The study was undertaken because of reports of increased fragments and chromosome breakage in individuals with AD. The study was performed blind on coded peripheral blood specimens, and the allocation of A D or control was not known to the cytogenetic staff until the end of the study. Both the AD group and the controls have been very carefully selected and both underwent the same clinical assessment and screening procedures which included C T scanning. Chromosomes were analysed after 72 hr cultures, using deprived medium TC199 which is known to enhance the appearance of fragile sites. A minimum of 50 cells was examined in each case, and any rearrangement found was classified as ctg, csg, ctb, csb and the chromosome in which it occurred was recorded. Analysis of results showed that there was no statistically significant difference between the A D group and the controls for either the total occurrence of breaks, the type of break or the chromosome(s) involved. In both groups the commonest break was at 3p, followed by a “satellited 16”.
CYTOGENETICS OF Ph’ NEGATIVE MYELOPROLIFERATIVE DISORDERS S. SINCHAND P. C . VINCENT Cytogenetics Unit, Medical Research Department, Kanematsu Memorial Institute, Sydney Hospital Between 1972 and 1982 the Cytogenetics Unit of Sydney Hospital received bone marrow and/or peripheral blood from 140 patients, believed to have a myeloproliferative disorder on clinical grounds. The P h ’ chromosome was seen in 63 of the patients, while the remaining 77 patients showed no Ph’ chromosome. Of these, 13 patients had polycythemia (all showing normal karyotypes), 15 had myelofibrosis
108
Pathology (1984), 16, January
I H F H U V A N CiENF'TIC'S SOCI[.TI' 01- 4L'STR.AL.ASI.A
( I 2 normal and 3 abnormal karyotypes). 33 had a myeloproliferative disorder (23 normal and 10 abnormal karyotypes) and 16 patients had il disorder which clinically and hematologically resembled chronic niyeloid leukemia (so-called Ph' negative CSlL). Ten of these patients showed a normal karyotype while in 6 it was abnormal. In 4 of the 6 Ph' negative CML patients with abnormal karyotype the disease was in an accelerated phase when first seen, while the other 2 went into an accelerated phase shortly afterwards. liaryotypic abnormalities in this sanlple both structural and numerical and were confined to C, D and G group chromosomes.
ANTE-NATAL DfAGNOSlS IN FAMILIES WITH 21 HYDROXYLASE DEFICIENCY 51. S . ST'I t k r j . J. B. HOL.IISTO\, G. GKNSIm , G . WILSOS. F. T. CriKr\Ti.\x\F\ \ X i ) R . L. D,\\\hr\S Deppnrrnieni o j Clinical l i t i i i i i ~ t ~ ~ Royal l ~ ~ . ~ Peril1 , ~ ~ . Hospital. H1.A t)ping o t culturcd amniotic. fibroblasts was done on 2 fetuses in related I'amilies who had one or more children with 21-OH deficiency. I h m the propositi, the 'affected' haplotypes were known to be AI. CW3, BWZZ and AlO, CWJ. BW22 in family I and A25, CLV3. BW22 and A3. C - , B M ' 4 i n famity II. H1.A typing of the amniotic cells was either by direct typing using two-colour fluorescence or a microabsorption technique as described by Pollack et al. Amniotic fluid 17-OH progesterone concentration \\a5 estimated by radioimmunoassay by the method of Boyne and Wilson. HLA typins o l t h e fetus in family 1 showed the presence of Al, A2 wsgestinp that the Fctus had one of the affected haplotypes (Al, CW3. BW22). The fetus in family II was found to have one of the affected haplotypes (A3, BW44). The amniotic fluid concentrations were 5 nmoliL (family I) and 4 nmolil. which excluded homozygous 21-hydrosylasedeficiency (normal range 2.3-7.3 nmoliL.). The k1L.A typing on both infants was confirmed post-natally using peripheral blood lymphocytes and standard NIH methods, suggesting that each infant was heterorggous for 21-OH deficiency, assuming no HLA-8. D recombination. Post-natal 17-OH progesterone estimation arid clinical eumination excluded homozygous ?I-OH deficiency.
THE FRAGILE X CHROMOSOME G~~~~~R. SUTHERLAND Department of Histopathology, The
Adelaide Children 3 Hospital
There will be a small working party sponsored by the National of Health held in Washington on 25-26 April, 1983, to discuss many
aspects of the fragile X. The author will have attended this meeting and will present a summary of current findings and research into the clinical. cytogenetic and molecular genetic aspects of the fragile X.
INDIVIDUAL VARIATION AND SPECIFIC COGNITIVE DEFICITS IN THE FRAGILE X SYNDROME THERESA M. THEOBALD AND DAVID A. HAY Lkpartment of Genetics and Human Variation. La Trobe University, Melbourne
While the fragile X is clearly associated with the X-linked mental retardation, two major behavioural questions have received little attention: (i) the extent and causes of individual variation in IQamong fragile X males and the possibility of some fragile X males being within the normal IQrange. (ii) whether there is a depression in general IQ or whether specific abilities are impaired, as would be likely if the disputed X-linkage of some spatial abilities does exist. These questions were examined in a sample of 53 fragile X males, their mothers who are obligate carriers and their sisters. Among noninstitutionalized males, performance IQranged from 100 to 0. while vocabulary scores ranged from 79-33. The result was that, unlike normal males, their verbal IQfar exceeded their performance IQ. Ability was unrelated to the proportion of cells with a fragile site-but correlated with mother's abilities. The males did exceptionally badly on a digit span task and only one male scored on the backward digit task. This deficit is specific to digits, since their performance on a memory for objects task was adequate. A similar pattern and variability emerged for institutionalized males, except that their abilities overall were much poorer. The mothers performed much better than the daughters, supporting the view that women who have children are a selected subset of the fragile X syndrome. Daughters were extremely variable in performance, which may relate to X chromosome inactivation.
ASSOCIATION OF HLA AND SKIN RESPONSE TO HISTAMINE 51. S. SlLI'hF'I, C . \vll-l, 1.. H. SCHVITT, %I. L.\TTI\IOHt.. R. H'.\RLO\\ .\\D R. 1.. U,\#hiw Ueparm?ent of Jtnmunolog~. Royal Perih Hospital U R Depurttiieni ~ of rltiaiotny and Human Biology, Universiry
of
Western .4ustrulici, Perrh
HLA and disease associations in man are not readily explicable in terms of immune response gene5 or molecular mimicry. Howe\er. evidence is accumulating that HLA genes are asrociated with variation in hormone concentrations or effects. Four hundred and twenty random participants in the 1981 Busselton Health survey were skin tested (prick testing) with 10-fold dilutions of histamine from 10 mg.'ml-' to 10-3m g m l - ' . HLA typing was done by the standard NIH method. The mean weal diametcr of subjects with H I A-€37 was greater than for non-U7 (P<0.005) for all histamine concentraticm except I@' mgiml-'. to which only 24 subjects responded. High frequency of positive responses was also seen in subjects with HLAA3. and IONfrequency in subjects with HLA-BIZ. However, the latter 2 association9 uerc shown by three-way contingency table analysis to be secondary to the association with HLA-B7. This exumplc provider further evidence that some HLA disease association9 may be mediated through an effect of HLA on hormone responsiveness. Further. it suggests that the expression of allergic disease is under the influence of multiple genes, since other factors such as total IgE concentration and specific allergen responsiveness are associated with different HLA phenotypes. or in the case of bronchial reactivity, not significantly associated with HLA.
SMALL SUPERNUMERARY CHROMOSOMES IN AMNIOTIC CELL CULTURES (TWO CASES) L. VOULLAIKE, M.SUSMAN ANDG.ALLEN Department of Luboratory Medicine, Queen Victoria Medical Cenlre. Melbourne
Small supernumerary chromosomes have been found in the normal population as well as in persons with congenital abnormalities and mental retardation. Consequently, the presence of small supernumaary chromosomes in amniotic cell cultures presents a problem in providing accurate prenatal diagnosis. This problem is stressed by 2 unrelated cases with small supernumerary chromosomes in amniotic cell cultures. The origin of the supernumerary chromosomes which appeared in all clones was investigated with various banding techniques, including GTG, CBG, NOR-Ag staining and DAPl staining. In one case the chromosome was bisatellited indicating its acrocentric origin. The pregnancy continues. In the second case the small size of the chromosome did not allow the identification of a specific pattern. The pregnancy was terminated, with a phenotypically normal fetus. In both these cases the parental karyotypes are normal. The poster will illustrate the morphology of supernumerary chromosomes and their banding characteristics.