Figure 1

(A) Serial chest radiographs of the patient. The chest X-ray films taken at other hospitals in 1996 reveal infiltration in both the upper and lower lobes in April, and in the lower lobe of the right lung in November. The chest radiograph on admission to our hospital in June 1997 demonstrates infiltration in the left lower lobe and the existence of pleural effusion. (B) Flow cytometric analysis of BTK expression in peripheral monocytes. The solid and the dashed lines indicate cells stained with anti-BTK or control antibody, respectively. FITC, Fluorescein isothiocyanate. (C) The genomic organization of the human BTK gene and the domain structure of BTK cDNA. Exons 1–19 of the BTK gene, and the BTK cDNA with its functional domains are shown [14]. Amino acid numbers (1–659) are shown under the cDNA. The arrowhead indicates the position of the mutation identified in this case. 5UT, 5'-untranslated region; PH, pleckstrin homology domain; TH, Tec homology domain; SH, Src homology domain; 3UT, 3'-untranslated region. (D) Detection of a 2 base pair deletion in the BTK cDNA. The BTK cDNA of the patient was sequenced as described in Materials and methods. The chromatograph of the autosequencer shows a 2 base pair deletion. (E) Family pedigree and the PCR-based detection of the mutated allele. Two generations are depicted. The index case is marked by an arrow. Genomic DNAs from the patient, his mother and his brother were extracted from peripheral blood and amplified by PCR using either primer A or primer B, together with the common downstream primer C. Normal genomic DNA gave a band when primer A was used (lane N). The patient's DNA gave a band when primer B was used (lane D). The patient's mother, a carrier of the mutated gene, gave bands when both primers A and B were used (lanes N and D).