Molecular analysis of a translocation (6;11)(p21;q25) in a girl with Jacobsen syndrome.

More than 70 patients with Jacobsen syndrome have been described [Penny et al., 1995; Pivnick et al., 1996; Ono et al., 1996]. The Jacobsen syndrome comprises mild to moderate psychomotor retardation, trigonocephaly, minor facial anomalies, cardiac defects, and thrombocytopenia. The syndrome is caused by distal deletions of chromosome arm 11q, including 11q24.1. Until now, no clear correlation between genotype and phenotype could be established. Recently, Michaelis et al. [1998] showed that in most cases in which the breakpoint was distal to marker D11S924, the deleted chromosome was paternal in origin. We describe a patient with Jacobsen syndrome, due to a de novo translocation (6;11)(p21;q25). The affected girl was born at 40 weeks of gestation to a 31-year-old father and a 30-year-old mother. The nonconsanguineous parents and an older sib were healthy. The pregnancy was uneventful, but delivery was by Cesarean section because of a breech presentation. Birth weight was 2,710 g (50th centile) and Apgar scores were 6, 8, and 10 at 1, 5, and 10 minutes, respectively. Neonatally there were feeding difficulties and hypoglycemia. At physical examination a systolic cardiac murmur and enlargement of liver and spleen were found. Facial abnormalities consisted of slight frontal bossing, bitemporal narrowness, capillary hemangioma on the forehead, broad nasal bridge, dystopia canthorum, downward slant of palpebral fissures, convergent strabismus, long philtrum, small upper lip, broad mouth with down-turned corners, broad alveolar ridges, high palate, simple formed helices, simian creases, and proximal-placed thumbs (Fig. 1). Cardiac sonography showed a severe ventricularand atrial septal defect and a patent ductus arteriosus. A computed tomography scan of the head showed slight enlargement of the Sylvian fissure and increased extracerebral spinal fluid. The urogenital tract was sonographically normal. On laboratory examination a thrombocytopenia was noted (38 × 109/l). The other hematological values were normal, and therefore a bone marrow aspiration was not performed. Results of ex-