title: A syndrome involving intrauterine growth retardation, microcephaly, cerebellar hypoplasia, B lymphocyte deficiency, and progressive pancytopenia.
abstract: We report a new complex syndrome involving profound failure to thrive with severe intrauterine growth retardation, cerebellar abnormalities, microcephaly, a complete lack of B lymphocyte development, and secondary, progressive marrow aplasia. B cell differentiation was found to be blocked at the pro-B cell stage. Although not strictly proven, a genetic origin is likely, according to similar cases reported in the literature. Three candidate genes, PAX5, encoding B cell-specific activator protein, a factor involved in B cell lineage commitment, stromal cell-derived factor 1, and CXCR4, encoding a chemokine and its receptor, respectively, were thought to be responsible for this disease, given the similarity between the phenotype of the corresponding knock-out mice and the clinical features of the patient. However, the genomic DNA sequences of these 3 genes were normal, and normal amounts of stromal cell-derived factor 1 and CXCR4 were present. These data strongly suggest that another molecule is involved in early B cell differentiation, hematopoiesis, and cerebellar development in humans.
authors.affiliation: INSERM U429, Hôpital Necker-Enfants-Malades, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Revy
authors.forename: M
authors.initials: M
authors.lastname: Busslinger
authors.forename: K
authors.initials: K
authors.lastname: Tashiro
authors.forename: F
authors.initials: F
authors.lastname: Arenzana
authors.forename: P
authors.initials: P
authors.lastname: Pillet
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Durandy
mesh_terms: D000361:Agammaglobulinemia / Q000151:congenital / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002531:Cerebellum / Q000002:abnormalities*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008831:Microcephaly / Q000235:genetics; D051757:PAX5 Transcription Factor; D010198:Pancytopenia / Q000151:congenital* / Q000235:genetics; D011506:Proteins / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D011506:Proteins; D019718:Receptors, CXCR4; D014157:Transcription Factors