Quantitative real-time polymerase chain reaction (RQ-PCR) for the rapid detection of SHOX haploinsufficiency in Leri-Weill Syndrome.

The short stature homeobox-containing (SHOX) gene, found on the human sex chromosomes, has a role in bone growth and height determination. Haploinsufficiency of the SHOX gene is believed to be responsible for poor growth such as that observed in ther Leri-Weill syndrome (LWS). This is the first report of the study of SHOX gene copy number by the technique of quantitative real-time polymerase chain reaction (RQ-PCR) in 9 patients with LWS. Only 7 patients (78%) of LWS had one copy of the SHOX gene deleted, but 2 patients (12%) have neither a single copy gene deletion nor point mutation after direct sequencing of all 7 exons. Although the majority of patients with LWS in this study have SHOX gene haploinsufficiency, there are some patients with both copies of the SHOX gene intact with absence of any point mutations in the coding region. This may be due to abnormalities in the upstream promoter, or to the effect of other candidate gene mutations. RQ-PCR is a faster and cheaper method of studying SHOX sing-copy deletions compared with the conventional fluorescence in situ hybridization (FISH), and is recommended for the detection of SHOX gene haploinsufficiency.