|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
RED CELLS
From the INSERM U473, Le Kremlin-Bicêtre,
France; Laboratoire d'Hématologie,
d'Immunologie et de Cytogénétique, Hôpital de
Bicêtre, Assistance Publique-Hôpitaux de Paris,
Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre,
France; Laboratoire de Biochimie I, Hôpital de
Bicêtre, Le Kremlin-Bicêtre, France;
Laboratoire de Biologie Spécialisée, Hôpital de
Bicêtre, Le Kremlin-Bicêtre, France;
Laboratoire de Biologie Moléculaire, Faculté de Pharmacie,
Université Paris V, Paris, France; Service de
Pédiatrie Générale, Hôpital de Bicêtre,
Le Kremlin-Bicêtre, France; INSERM U 409, Faculté de Médecine Xavier-Bichat, Paris,
France; Service d'Hématologie, Hôpital
Michallon, Grenoble, France; Service d'Hématologie,
Hôpital Necker-Enfants-Malades, Paris, France;
Hospital Laboratories and Clinical Pathology, University of
Massachusetts Medical Center, Worcester, MA; Department of
Medicine, Cardeza Foundation for Hematologic Research,
Philadelphia, PA; INSERM U 292, Le Kremlin-Bicêtre,
France; INSERM U 535, Le Kremlin-Bicêtre,
France; Department of Medicine, University College,
London, UK; Servizio di Genetica Medica, IRCCS-Casa
Sollievo Soflerenza, San Giovanni Rotondo, Italy;
Dipartimento di Biomedicina dell' Età Evolutiva,
Università degli Studi di Bari, Bari, Italy.
Dehydrated hereditary stomatocytosis (DHS) is a rare genetic
disorder of red cell permeability to cations, leading to a
well-compensated hemolytic anemia. DHS was shown previously to be
associated in some families with a particular form of perinatal edema,
which resolves in the weeks following birth and, in addition, with
pseudohyperkalemia in one kindred. The latter condition was hitherto
regarded as the separate entity, "familial pseudohyperkalemia." DHS
and familial pseudohyperkalemia are thought to stem from the same gene,
mapping to 16q23-q24. This study screened 8 French and 2 American
families with DHS. DHS appeared to be part of a pleiotropic syndrome in some families: DHS + perinatal edema, DHS + pseudohyperkalemia, or DHS + perinatal edema + pseudohyperkalemia. If adequately attended to, the perinatal edema
resolved spontaneously after birth. Logistic regression showed that
increased mean corpuscular volume and mean corpuscular hemoglobin
concentration were the parameters best related to DHS. In patients in
whom cation fluxes were investigated, the temperature dependence of the
monovalent cation leak exhibited comparable curves. Specific
recombination events consistently suggested that the responsible gene
lies between markers D16S402 and D16S3037 (16q23-q24). The 95%
confidence limits (Zmax Genetic disorders of the red cell membrane
permeability to Na+ and K+ account for a number
of rare hereditary hemolytic anemias, characterized by an increased
passive leak of the monovalent cations Na+ and
K+. The intraerythrocytic cation concentrations can be
altered to various extents, as well as cell hydration and
morphology.1 Hereditary dehydrated stomatocytosis (DHS)
(OMIM 194380),2-3 or hereditary xerocytosis, usually
appears as a well-compensated chronic hemolysis. Familial
pseudohyperkalemia (OMIM 177720) is characterized by an increase of the
K+ concentration in plasma when freshly drawn blood is
allowed to stand at temperatures lower than 37°C. It is devoid of
hematologic symptoms.4-9 DHS and pseudohyperkalemia have a
dominant inheritance pattern.
Dehydrated hereditary stomatocytosis has long been regarded as a purely
hematologic condition.2,3,10-17 The osmotic resistance is
increased and the osmotic gradient ektacytometric curve shows a
leftward shift.1,18,19 Splenectomy dramatically increases the thromboembolic risk.20 Recently, DHS was shown to be
part of a broader syndrome (OMIM 603528) in some families where it was
associated with a particular form of perinatal edema,21,22 which will be designated PEDHS.
Pseudohyperkalemia22 could also be present. Although DHS
and pseudohyperkalemia are lifelong manifestations, PEDHS
resolves within weeks or months after birth (if not before). We
hypothesized22 that the present pleiotropic syndrome would stem from the same gene. That the genes presumably responsible for both
DHS and familial pseudohyperkalemia were found to map to
16q23-qter23,24 supported the one-gene hypothesis.
In 10 families, we reassessed the hematologic presentation of
DHS. We compiled the various combinations of symptoms within the
pleiotropic syndrome and evaluated the phenotypical variations that
occurred within some kindreds. The temperature dependence of the
monovalent cation leak was found comparable under distinct clinical
presentations. Specific recombination events consistently suggested
that the responsible gene lay between markers D16S402 and D16S3037
(16q23-q24) in a 9-cM interval.
Kindreds
The classification of kindreds was established based on the maximum
number of manifestations recorded (Figure 2). We are aware of the fact
that we could underclassify some families for having missed, for
example, the only member with pseudohyperkalemia in one kindred.
PEDHS could be overlooked, had it been restricted to a mild
edema and to the prenatal period, before ultrasound was available. No
case of PEDHS could be found in 7 families. In each of the
other 3 families, there was 1 stillborn fetus and 1 or 2 living members
with antecedents of PEDHS.
Red cell indices and reticulocyte counts
Assessment of pseudohyperkalemia
Some families were seen in our department and blood incubations for kalemia determination were started on site. When field trips were necessary, whole blood incubations were performed locally. At the end of the incubations (as described above), the recovered plasma aliquots were temporarily secured at 4°C (4-8 hours) until they reached our department. Under such conditions, kalemia could undergo no further change because sera and erythrocytes had been separated. The 2 American families were not included in this protocol. Other methods (not shown) pleaded against pseudohyperkalemia in family PH. No tests were available as regards family WO. Determination of intraerythrocytic cation concentrations and cation flux rates across the membrane Blood samples (10 mL, citrate-phosphate-dextrose [CPD]-adenine tubes, 4°C) were shipped to London immediately after venisection. Intracellular electrolytes were measured as described.31 A travel control was included with samples from VE and VA. Travel controls showed a rise in [Na+] and a fall in [K+] of 3 to 5 mmol/L cells during overnight storage on ice in CPD (Chetty and Stewart, unpublished observations). Isotopic fluxes were determined using 86Rb+ as a tracer for K+ in a NaCl/MOPS/glucose solution, containing (concentration expressed in mmol/L): Na+, 145; K+, 5; Cl , 150; MOPS-Na+, 15 (pH
7.4 at room temperature); glucose, 5; and ouabain and/or bumetanide,
0.1 each, if required (ouabain and bumetanide inhibit the
Na+ pump and the Na+, K+
cotransporter, respectively). The temperature dependence of the K+ leak (eg, the monovalent cation passive leak) was
established by measurement of the ouabain + bumetanide-resistant
86Rb+ influx as a function of temperature in
the same solution.31
Microsatellite analysis Analyses were performed using microsatellites slightly different from those used before23: D16S511, D16S402, D16S3061 (optional), D16S3037, D16S520, D16S498, and D16S3074. Their order from centromere to telomere and the genetic distances between them were derived from several online databases.32 In some cases, marker D16S3037 did not bring any information because family members were homozygotes. We then used marker D16S3061, centromeric yet close (0.1 cM) to marker D16S3037 (Figure 1, Inset A). We were not aware of other microsatellites in the D16S402-D16S3037 interval. The polymerase chain reaction (PCR) products were monitored in a ABI Prism 377 DNA Sequencer (Applied Biosystems, Foster City, CA). Results were processed through Genescan Software. The PCR was performed twice and fragment lengths measured on different gels.Linkage analysis was performed on the basis of an autosomal dominant
disease with a penetrance of 95%. This value was chosen in
consideration of the 2 symptomless individuals (members I.1 and III.6
from family GR) thought to carry the DHS-associated haplotype (see
below), and the 37 patients. Family BI was noninformative. The
disease-gene frequency was set to 0.0012 as previously
described,23 and the marker alleles frequencies were
calculated from the parental allele repartition. Multipoint linkage was
performed by use of the GENEHUNTER software package.33 The
approximate 95% confidence limits for the maximum recombination
fraction (
The hematologic picture The term DHS will refer solely to the hematologic manifestations, including those evidenced by ektacytometry, and irrespective of the presence or absence of other manifestations. In general, hemoglobin was nonsignificantly diminished, whereas the reticulocytes were markedly increased, indicating a well-compensated anemia (Figure 3). There was a definite tendency toward macrocytosis. The mean corpuscular hemoglobin concentration (MCHC) was significantly increased; however, hyperdense cells (MCHC > 41g/dL) failed to appear as significantly increased (threshold, 4%) (not shown). Logistic regression showed that MCHC and mean corpuscular volume (MCV) were the most significantly linked to DHS (odds ratios: 5.5 and 1.3, respectively, with P = .003 and P = .004, respectively). SDS-PAGE showed a normal profile in all the affected members who were investigated within each family (not shown).
The osmotic gradient ektacytometric curve was shifted to the left
(Figure 4). The deformability index
remained within the normal range. The leftward displacement of the O'
point indicated cellular dehydration. The leftward displacement of
Omin witnessed an increase of the red cell surface
area/volume ratio. It appeared as the most consistent parameter in DHS.
Four affected patients underwent splenectomy as a treatment for their hemolytic disease. Long-term follow-up revealed the occurrence of thromboembolic complications in all of them. Patient II.2 from family AR, splenectomized at the age of 15, sustained a deep venous thrombosis at the age of 24. Patient II.2 from family DA, also splenectomized at the age of 15, developed a portal vein thrombosis 8 days later.35 Patient I.1 from family TR (who probably had DHS) died at the age of 32 of pulmonary thrombotic complications in the postsplenectomy period. Patient I.1 from family VE, splenectomized at the age of 44, suffered from recurrent episodes of superficial and deep venous thrombosis (once a year for 11 years and then less frequently), leading to severe venous ulceration in the lower limbs. These manifestations are consistent with the report by Stewart and coworkers20 and confirm that splenectomy is hazardous in DHS. DHS as part of a pleiotropic syndrome; intrafamilial phenotypical variations in some kindreds PEDHS has occurred in at least one living member of families BI, GR, and VE, and stillborn antecedents were present in each of these kindreds. Pseudohyperkalemia appeared in 4 of 8 tested families (families AR, BI,22 CL, and VA) (Figure 2). The presentation of the pleiotropic syndrome was not immutable within all kindreds. In some of them, we observed that any manifestation, the hematologic symptoms, PEDHS or pseudohyperkalemia, could vary on an intrafamilial basis, as detailed in the following.The hematologic symptoms were missing or strongly reduced in some members even though they carried the DHS-associated haplotype. In family DA, member II.2 had conspicuously disturbed red cell parameters (and thrombotic antecedents), whereas only MCV, Omin, and O' were slightly altered in member I.1. In family GR, member III.1, the proband, had an unmistakable DHS. (Member IV.1 [unmistakable PEDHS] is not described here in detail.) Other members had strongly reduced hematologic symptoms yet they displayed, at the very least, a leftward shift of the Omin point at the ektacytometer. On the other hand, members I.1 and III.6 failed to even exhibit this feature. Member III.4 was in the same situation but, instead, she had had a perinatal edema (see above) offering a distinct facet of the pleiotropic syndrome. In families BI, the occurrence of PEDHS was constant,
whereas it was inconstant in families GR and VE as far as we could
document. Plasma K+ values (after 6 hours of incubation at
20°C) were above normal only in all DHS members from families BI and
VA, but only in some within kindreds AR and CL (Figure
5).
The cation leak Measurements of intracellular Na+ and K+ concentrations and of flux rates are shown in Table 1. All values obtained were consistent with previously reported results for DHS.22,23 Individual GR III.1, however, showed normal intracellular Na+ and K+ concentrations, even after storage in the cold, but the isotopic flux rates showed a clearly increased ouabain + bumetanide-resistant K+ leak, and a strikingly elevated Na+, K+ pump rate at about 6 times normal, which can explain why the intracellular Na+ concentration was not high. In the temperature studies, all kindreds tested (CL, GR, VA, VE) showed increased fluxes at 37°C, and the temperature profiles fell within a narrow envelope that is essentially parallel to normal in these cases (Figure 6).
Microsatellite analysis In the 10 investigated families, the location of the responsible gene was consistent with 16q23-q24 (Figure 1). Some crossover events repeatedly took place between microsatellites D16S402 and D16S3037. When some uncertainty remained about segregation of D16S3037, marker D16S3061, 0.1 cM centromeric to marker D16S3037, was used. For example, in family VE, one could not decide which of the 2 D16S3037 alleles (210 bp/210 bp) had been transmitted from the father (member I.1) to one of his sons (member II.3). Use of marker D16S3061 showed that it was subhaplotype D16S3061-D16S3037-D16S520-D16S498-D16S3074 (249-210-183-220-193 bp) that had been passed on en bloc.In family GR, the fact that DHS had no penetrance in one member of the oldest generation (member I.1 or I.2) rendered difficult the interpretation of the haplotypes. Backing up from generation III (member III.1: overt DHS; member III.4: PEDHS) through generation II (DHS weakly expressed), a highly plausible haplotype pattern including crossover events was found. It implied that members I.1 and III.6 would carry the DHS-associated haplotype. These 2 extreme and puzzling cases led us to equal the penetrance of the condition to 95% in the study. Crossover events occurring in the D16S402-D16S3037 (9-cM) interval
appeared consistently either centromeric (family VE) or telomeric
(families GR and TR) to the gene (Figure 1, Inset B). Significant lod
scores (Zmax
Spurred by initial observations by Entezami and colleagues21 and ourselves,22 the aims of this work were to (1) revisit the hematologic picture of DHS, (2) define how DHS was part of a broader syndrome including PEDHS or pseudohyperkalemia and assess the phenotypical variations observed within some kindreds, (3) evaluate the alteration of the cation leak, and (4) determine whether the responsible gene would in all kindreds map to 16q23-q24.23 The hematologic picture We confirmed that red cell parameters can give a substantial hint at the diagnosis: well-compensated hyperhemolysis, high reticulocyte count, increased MCV and MCHC, but a variable increase in the percentage of hyperdense cells. Specifically, logistic regression showed that MCHC and MCV were the parameters most significantly linked to DHS. Osmotic gradient ektacytometry yielded the most consistent information through the leftward shift of Omin point. In the absence of available ektacytometry, increase in the osmotic resistance, measured on fresh blood, would be the best diagnostic test to detect DHS. The Omin point (osmolality at which the red cells are maximally swollen in ektacytometry) corresponds to the 50% hemolysis point in the fragility osmotic testing.DHS as part of a pleiotropic syndrome; intrafamilial phenotypical variations in some kindreds The presentation of the pleiotropic syndrome was not immutable within all kindreds. We observed that any manifestation, the hematologic symptoms, PEDHS and pseudohyperkalemia, could vary on an intrafamilial basis. The most compelling case was provided by family GR. Member III.1 presented with typical hematologic symptoms but no known history of PEDHS, and her cousin (member III.4) had had a plain history of PEDHS but displayed no hematologic manifestations.PEDHS deserves special comments. It would be a mistake to
infer a cause-to-effect relationship between fetal edema and fetal anemia (by analogy with immune hydrops fetalis that follows severe Homogeneity of red cell cation abnormalities All kindreds tested showed typical abnormalities of intracellular Na+ concentrations and flux rates, as defined for DHS,23 with the exception of family GR. Family GR showed near normal intracellular Na+ and K+ concentrations, whereas the flux rates indicated a significant cation leak with a more than usually obvious increase in the Na+, K+ pump rate. The explanation for this is unclear. This illustrates that it is not possible to exclude the presence of "leaky red cells" on the basis of measurement of intracellular Na+ and K+ concentrations alone, without recourse to flux rate measurement as well. As for the temperature dependence of the cation leak, all members tested exhibited a comparable curve that was simply shifted up the y-axis compared to normal, as seen previously in an Irish family with DHS.23,36 Altogether, despite some variations, it appeared that the cation leak essentially showed similar patterns whatever the status of DHS, alone or part of a broader syndrome. This pattern is close also to that encountered in chromosome 16-related familial pseudohyperkalaemia.24 On the other hand, it clearly departed from that found in a variant form of hereditary stomatocytosis with pseudohyperkalemia.31The genetic homogeneity In all kindreds tested, mapping of the responsible gene was consistent with 16q23-q24. This supports the view that the DHS pleiotropic syndrome is a monogenic syndrome. Specific crossover events suggested that the responsible gene would lie between markers D16S402 and D16S3037 (or D16S3061 if tested). In previous studies, Carella and coworkers23 and Iolascon and colleagues24 used 2-point linkage analysis. The latter did not allow assessment of how likely was the presence of a gene over the whole interval between 2 particular markers. The crossover events exhibited by the Irish DHS family, referred to as family A,23 were comparable to those observed in family VE presented here. In the present study, using a multipoint linkage analysis, the 95% confidence limits (Zmax 3.02) spanned almost the complete 9-cM
interval between markers D16S402 and D16S3037.
The kindreds do not share a common haplotype because they are unrelated in all likelihood. PEDHS was expressed in member II.5 from family VE (along with DHS) who carries telomeric subhaplotype (D16S402, D16S3061, D16S3037, D16S520, D16S498, and D16S3074). It was also expressed in member IV.1 (not detailed here) from family GR who carries the restricted centromeric subhaplotype (D16S511, D16S402). These 2 cases matched with a D16S402-D16S3037 interval location of the PEDHS locus, just as they do for DHS itself. Therefore, it is doubtful whether a second locus would come into play as for PEDHS. This study agrees with the works by Innes and associates37
that excluded a linkage of DHS with the In this work, a complete account of the DHS hematologic phenotype was
provided in 10 families. DHS appeared to be part of a pleiotropic
syndrome, including perinatal edema and pseudohyperkalemia in some
kindreds. We further showed intrafamilial phenotypical variations in
some kindreds. The monovalent cation passive leak displayed comparable
patterns whatever the symptoms. Finally, specific recombination events
and lod score calculations consistently suggested that the responsible
gene would lie between markers D16S402 and D16S3037 in a 9-cM interval
(16q23-q24) (Zmax
We are grateful to the investigated families for their kind cooperation. We thank Dr M. C. Chetty, Dr F. Clerget, Pr A. Spira, and Pr M. Vidaud for their critical advice, and also Ms. M. Dehan and Dr F. Baklouti for their careful reading of the manuscript. Clinician and laboratory investigators having participated in the work: Dr C. Barro (Hôpital Michallon, Grenoble, France), Dr J.-P. Blondel (Laboratoire de Biologie Médicale, Arras, France), Drs B. Cantelou and F. Lifermann (Centre Hospitalier, Dax, France), Drs B. Coupe, P. Saladin, and P. Thierry (Centre Hospitalier Paul-Morel, Vesoul, France), Dr G. Dine (Centre Hospitalier, Troyes, France), and Dr R. A. Drachtman (Robert Wood Johnson University Hospital, NJ).
Submitted December 2, 1999; accepted May 25, 2000.
Supported by the Institut National de la Santé et de la Recherche Médicale (Unité 473), the Fonds d'Etudes et de Recherche du Corps Médical de l'Assistance Publique-Hôpitaux de Paris, the Délégation à la Recherche Clinique de l'Assistance Publique-Hôpitaux de Paris (CRC96082), the Fondation pour la Recherche Médicale, the Faculté de Médecine Paris-Sud (France), the Telethon Projects E-645 and E-743, the MURST, the Ministero Italiano delle Sanità (Italy), and by Action Research and the WELLCOME Trust (UK).
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Sabine Grootenboer, INSERM U 473, 84 rue du Général-Leclerc, 94276 Le Kremlin-Bicêtre, France; e-mail: delaunay{at}kb.inserm.fr.
1. Delaunay J, Stewart G, Iolascon A. Hereditary dehydrated and overhydrated stomatocytosis: recent advances. Curr Opin Hematol. (Narla M, ed ; Current Science). 1999;6:110-114[Medline] [Order article via Infotrieve].
2.
Miller DR, Rickles FR, Lichtman MA, La Celle PL, Bates J, Weed RI.
A new variant of hereditary hemolytic anemia with stomatocytosis and erythrocyte cation abnormality.
Blood.
1971;38:184-204 3. Glader BE, Fortier N, Albala MM, Nathan DG. Congenital hemolytic anemia associated with dehydrated erythrocytes and increased potassium loss. N Engl J Med. 1974;291:491-496. 4. Stewart GW, Corrall RJM, Fyffe JA, Stockdill G, Strong JA. Familial pseudohyperkalaemia. Lancet. 1979;28:175-177. 5. Luciani JC, Lavabre-Bertrand T, Fourcade J, Barjon P, Mimran A, Callis A. Familial pseudohyperkalaemia. Lancet. 1980;1i:491[Medline] [Order article via Infotrieve]. 6. Leadbeatter S, O'Dowd TC. Possible screening test for familial pseudohyperkalaemia. Lancet. 1982;10:103-104. 7. Naidu R, Steg NL, MacEwen GD. Hyperkalemia: benign, hereditary, autosomal dominant. Anesthesiology. 1982;56:226-228[Medline] [Order article via Infotrieve]. 8. Enet-Renou N, Mirouze J, Dagher G, Dupont M, Richard JL, Mimran A. Pseudo-hyperkaliémie d'origine érythrocytaire. Augmentation passive de la perméabilité membranaire du potassium. Pathol Biol. 1983;31:583-588[Medline] [Order article via Infotrieve]. 9. Vantyghem MC, Dagher G, Doise B, et al. Pseudo-hyperkaliémie. A propos d'une observation familiale. Ann Endocrinol (Paris). 1991;52:104-108[Medline] [Order article via Infotrieve].
10.
Snyder LM, Lutz HU, Sauberman N, Jacobs J, Fortier NL.
Fragmentation and myelin formation in hereditary xerocytosis and other hemolytic anemias.
Blood.
1978;52:750-761 11. Harm W, Fortier NL, Lux HU, Fairbanks G, Snyder LM. Increased erythrocyte peroxidation in hereditary xerocytosis. Clin Chim Acta. 1979;99:121-128[Medline] [Order article via Infotrieve]. 12. Sauberman N, Fairbanks G, Lutz HU, Fortier NL, Snyder LM. Altered red blood cell surface area in hereditary xerocytosis. Clin Chim Acta. 1981;114:149-161[Medline] [Order article via Infotrieve]. 13. Snyder LM, Sauberman N, Condara H, et al. Red cell membrane response to hydrogen peroxide-sensitivity in hereditary xerocytosis and in other abnormal red cells. Br J Haematol. 1981;48:435-444[Medline] [Order article via Infotrieve]. 14. Platt OS, Lux SE, Nathan DG. Exercise-induced hemolysis in xerocytosis. Erythrocyte dehydration and shear sensitivity. J Clin Invest. 1981;68:631-638.
15.
McGrath KM, Collecutt MF, Gordon A, Sawers RJ, Faragher BS.
Dehydrated hereditary stomatocytosis 16. Fey MF, Bischof M, Zahler P, Schatzmann HJ, Bucher U. Hereditary leaky red cell syndrome in a Swiss family. Acta Haematol. 1986;75:70-78[Medline] [Order article via Infotrieve]. 17. Vives-Corrons J Ll, Besson I, Aymerich M, et al. Hereditary xerocytosis: a report on six unrelated Spanish families with leaky red cell syndrome and increased heat stability of the erythrocyte membrane. Br J Haematol. 1995;90:817-822[Medline] [Order article via Infotrieve].
18.
Clark MR, Mohandas N, Shohet SB.
Osmotic gradient ektacytometry: comprehensive characterization of red cell volume and surface maintenance.
Blood.
1983;61:899-910 19. Johnson RM, Ravindranah Y. Osmotic scan ektacytometry in clinical diagnosis [review article]. J Pediatr Hematol Oncol. 1996;18:122-129[Medline] [Order article via Infotrieve]. 20. Stewart GW, Amess JAL, Eber SW, et al. Thrombo-embolic disease after splenectomy for hereditary stomatocytosis. Br J Haematol. 1996;93:303-310[Medline] [Order article via Infotrieve].
21.
Entezami M, Becker R, Menssen HD, Marcinkowski M, Versmold HT.
Xerocytosis with concomitant intrauterine ascites: first description and therapeutic approach [correspondence].
Blood.
1996;87:5392-5393 22. Grootenboer S, Schischmanoff PO, Cynober T, et al. A genetic syndrome associating dehydrated hereditary stomatocytosis, pseudohyperkalaemia and perinatal oedema. Br J Haematol. 1998;103:383-386[Medline] [Order article via Infotrieve]. 23. Carella M, Stewart G, Ajetunmobi JF, et al. Mapping of dehydrated hereditary stomatocytosis (hereditary xerocytosis) locus to chromosome 16 (16q23-qter) by genome wide search. Am J Hum Genet. 1998;63:810-816[Medline] [Order article via Infotrieve].
24.
Iolascon A, Stewart GW, Ajetunmobi JF, et al.
Familial pseudohyperkalemia maps to the same locus as dehydrated hereditary stomatocytosis (hereditary xerocytosis).
Blood.
1999;93:3120-3123 25. Bessis M, Mohandas N, Féo C. Automated ektacytometry: a new method of measuring red cell deformability and red cell indices. Blood Cells. 1980;6:315-327[Medline] [Order article via Infotrieve]. 26. Cynober T, Mohandas N, Tchernia G. Red cell abnormalities in hereditary spherocytosis: relevance to diagnosis and understanding of the variable expression of clinical severity. J Lab Clin Med. 1996;128:259-269[Medline] [Order article via Infotrieve]. 27. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680-685[Medline] [Order article via Infotrieve]. 28. Fairbanks G, Steck TL, Wallach DFH. Electrophoresis analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry. 1971;10:2606-2617[Medline] [Order article via Infotrieve].
29.
Alloisio N, Texier P, Denoroy L, et al.
The cisternae decorating the red blood cell membrane in congenital dyserythropoietic anemia (type II) originate from the endoplasmic reticulum.
Blood.
1996;87:4433-4439 30. Taulier A, Levillain P, Lemonnier A. Intérêt de la spectrophotométrie dérivée pour le dosage de l'hémoglobine plasmatique et urinaire. Ann Biol Clin. 1986;44:242-248. 31. Coles SE, Ho MH, Chetty MC, Nicolaou A, Stewart GW. A variant of hereditary stomatocytosis with marked pseudohyperkalaemia. Br J Haematol. 1999;104:275-283[Medline] [Order article via Infotrieve].
32. National Center for Biotechnology Information. Genemap'99,
available at
http://www.ncbi.nlm.nih. 33. Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996;58:1347-1363[Medline] [Order article via Infotrieve]. 34. Ott J. Analysis of Human Linkage. 2nd ed. Baltimore, MD: Johns Hopkins University Press; 1992. 35. Perel Y, Dhermy D, Carrere A, et al. Portal vein thrombosis after splenectomy for hereditary stomatocytosis in childhood. Eur J Pediatr. 1999;58:628-630. 36. Stewart GW. The membrane defect in hereditary stomatocytosis. In: Tanner MJA,Anstee DJ, eds. Red Cell Membrane Antigens. London, UK: Baillière's-Tyndall; 1993:371-399.
37.
Innes DS, Sinard JH, Snyder LM, Gallagher PG, Morrow JS.
Exclusion of the stomatin,
38.
Gallagher PG, Smith BD.
Dehydrated hereditary stomatocytosis is not linked to the h1H1 locus, a Gardos channel candidate, on chromosome 19q13.2 [correspondence].
Blood.
1999;93:2134-2135
39.
Carella M, Stewart G, Ajetunmobi JF, Schettini F Jr, Delaunay J, Iolascon A.
Genetic heterogeneity of hereditary stomatocytosis syndrome showing pseudohyperkalaemia [correspondence].
Haematologica.
1999;84:862-863
© 2000 by The American Society of Hematology.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|
 |
|
  A P Basu, P Carey, T Cynober, M Chetty, J Delaunay, G W Stewart, and S Richmond Dehydrated hereditary stomatocytosis with transient perinatal ascites Arch. Dis. Child. Fetal Neonatal Ed., September 1, 2003; 88(5): F438 - F439. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2000 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
Top
Abstract
Introduction
max) at Zmax
were calculated by the 1-lod-down method.
, patients; 
, symptomless family members.
(A) Hemoglobin was nonsignificantly decreased (P = .39).
(B) Reticulocytes were significantly increased
(P < .001). (C) MCV was significantly increased
(P < .001). (D) MCHC was significantly increased
(P < .001).
, families DHS
alone; 
,
family CL; 
, six controls; 
, family VA; 
,
family VE.
-thalassemia, for instance). Rather, DHS and PEDHS share
a relationship of coexistence with regard to the same genetic cause.
Treating anemia in utero was of no use to cure the
edema.
-adducin, and stomatin genes, and by Gallagher
and Smith,
3.02). Gene identification
is pending.
a report of two families and a review of the literature.
Pathology.
1984;16:146-150