TRANSLOCATION T(X-21)(Q13.3-P11.1) IN A GIRL WITH MENKES-DISEASE

A girl with a 46,X,t(X;21) (q13.3;p11.1) karyotype presented with skin redundancy, especially in the neck, prominent occiput and micrognathi a, and later developed hypotonia, hypopigmentation, sparse scalp hair, and profound mental retardation characteristic of Menkes disease. Her serum copper (14 mu g/dl) and ceruloplasmin (9 mg/dl) levels were ext remely low. Fluorescent in situ hybridization analysis with a 100-kb P 1-derived artificial chromosome probe containing the Menkes disease ge ne demonstrated three twin-signals, one on the normal X chromosome and one each on derivative chromosomes X and 21, indicating that the Xq13 .3 breakpoint was located within the gene. Replication pattern analysi s showed that the normal X chromosome was late replicating, whereas th e derivative X chromosome was selectively early replicating, These res ults indicated that Menkes disease in our patient resulted from a de n ovo translocation that disrupts the disease gene. (C) 1998 Wiley-Liss, Inc.