Congenital spherocytosis, B19 parvovirus infection and inherited interstitial deletion of the short arm of chromosome 8.
We report two siblings with congenital spherocytosis, multiple phenotypic abnormalities and an inherited interstitial deletion of the short arm of chromosome 8 (8p). The propositus came to our attention with acute bone marrow hypoplasia secondary to B19 parvovirus infection. The bone marrow trephine biopsy appearances of intranuclear eosinophilic degeneration in the erythroblasts may be pathognomonic of B19 parvovirus induced acute bone marrow aplasia. The presence of B19 parvovirus DNA was demonstrated in erythroblasts by in situ hybridization. Chromosome analysis of peripheral blood lymphocytes from both siblings showed an interstitial deletion of the short arm of chromosome 8, del (8) (p11p21). This abnormal chromosome was inherited from their mother, who showed this deletion as well as a small fragment representing the deleted 8p chromosome portion, del (8) (p11p21), +f. Centromeric material from chromosome 8 was detected in this chromosome fragment by in situ hybridization using an alpha satellite probe (pJM 128), but not by C banding. Chromosome analysis of skin fibroblasts from the mother and a third sibling with a similar karyotype showed the deleted fragment in over 80% of cells. Cells in which the fragment was absent exhibited the deleted 8p, suggesting there was no mosaicism. The mother and the third sibling were phenotypically normal without spherocytosis. A fourth sibling and the father were normal. The chromosome abnormality was not observed in five of the mother's siblings, suggesting that it arose de novo in the mother. Our findings strongly support a locus for congenital spherocytosis on the short arm of chromosome 8. The frequency of defects at this locus is unknown.
Cohen
H
H
Department of Haematology, University College, Middlesex School of Medicine, London.
Walker
H
H
Delhanty
J D
JD
Lucas
S B
SB
Huehns
E R
ER
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology; D001855:Bone Marrow Diseases / Q000209:etiology; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002898:Chromosomes, Human, Pair 8; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D010198:Pancytopenia / Q000209:etiology; D010321:Parvoviridae / Q000302:isolation & purification*; D010322:Parvoviridae Infections / Q000150:complications* / Q000175:diagnosis; D010375:Pedigree; D012698:Serologic Tests; D013103:Spherocytosis, Hereditary / Q000235:genetics*
D004279:DNA, Viral