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.
Ida
Tomoko
T
Kyushu Medical Science Nagasaki Laboratory, Nagasaki, Japan.
Miharu
Norio
N
Hayashitani
Michiko
M
Shimokawa
Osamu
O
Harada
Naoki
N
Samura
Osamu
O
Kubota
Takeo
T
Niikawa
Norio
N
Matsumoto
Naomichi
N
D000015:Abnormalities, Multiple / Q000235:genetics*; D000782:Aneuploidy; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D041321:Chromosomes, Human, X; D004303:Dosage Compensation, Genetic; D005260:Female; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D012729:Sex Chromosome Aberrations; D014178:Translocation, Genetic