Functional disomy for Xq22‐q23 in a girl with complex rearrangements of chromosomes 3 and X

A 5‐year‐old girl with developmental and growth retardation is reported with complex chromosome rearrangements consisting of a partial Xq deletion and an abnormal chromosome 3 with multiple breakpoints. GTG‐banding, and multiplex and conventional FISH studies showed that a 6.6‐Mb Xq22‐q23 segment was inserted into 3q, in addition to three intrachromosomal insertions in chromosome 3. Her karyotype was thus interpreted as 46,X,der(X)(Xpter→Xq22::Xq23→Xqter),der(3)(3pter→3p26::3p12→3q25.3::3p12→3p26::Xq22→Xq23::3q25.3→3qter). Replication R‐banding study showed that the der(X) was inactivated in all blood lymphocytes analyzed. Methylation‐specific PCR at the androgen receptor gene (HUMARA) locus at Xq11‐q12 showed a skewed inactivation pattern with the active/inactive X chromosome ratio of 92/8. These data indicated the presence, in the majority of cells, of a functioning Xq22‐q23 segment in both the normal X and the der(3) chromosomes. Her growth retardation, developmental delay, and other minor anomalies were most likely caused by dosage effects of the genes in the functionally disomic Xq22‐q23 region. Despite the presence of two active copies of the proteolipid protein 1 gene (PLP1), she did not show the symptoms of Pelizaeus‐Merzbacher disease, a subset of which has been known to be caused by the duplication of PLP1. © 2003 Wiley‐Liss, Inc.