@article{3081574,
    title = "Deletions of the homeobox gene SHOX (short stature homeobox) are an
important cause of growth failure in children with short stature",
    author = "Rappold, GA and Fukami, M and Niesler, B and Schiller, S and Zumkeller, and W and Bettendorf, M and Heinrich, U and Vlachopapadoupoulou, E and and Reinehr, T and Onigata, K and Ogata, T",
    journal = "JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM",
    year = "2002",
    volume = "87",
    number = "3",
    pages = "1402-1406",
    publisher = "ENDOCRINE SOC",
    issn = "0021-972X",
    doi = "10.1210/jc.87.3.1402",
    abstract = "Short stature, with an incidence of 3 in 100, is a fairly frequent
disorder in children. Idiopathic short stature refers to patients who
are short due to various unknown reasons. Mutations of a human homeobox
gene, SHOX (short stature homeobox), have recently been shown to be
associated with the short stature phenotype in patients with Turner
syndrome and most patients with Leri-Weill dyschondrosteosis. This study
addresses the question of the incidence and type of SHOX mutations in
patients with short stature. We analyzed the SHOX gene for intragenic
mutations by single strand conformation polymorphism, followed by
sequencing, in 750 patients and for complete gene deletions by
fluorescence in situ hybridization in 150 patients (total, 900
patients). This is the largest group of patients with short stature
studied to date for SHOX mutations. All patients had a normal karyotype,
and their height for chronological age were below the third percentile
or minus 2 SD of national height standards. All were without obvious
skeletal features reminiscent of the Leri-Weill syndrome at the time of
diagnosis.
Silent, missense, and nonsense mutations and a small deletion in the
coding region of SHOX were identified in 9 of the 750 patients analyzed
for intragenic mutations. Complete gene deletions were detected in 3 of
the 150 patients studied for gene deletions. At least 3 of the 9
intragenic mutations were judged to be functional based upon the
genotype-phenotype relationship for the parents and normal control
individuals. We conclude that SHOX mutations have been detected in 2.4%
of children with short stature. The spectrum of SHOX mutations is
biased, with the vast majority leading to complete gene deletions. The
prevalence of short stature due to SHOX gene mutations among children
with short stature appears to be similar to that of GH deficiency or
Turner syndrome. Family studies of the children with SHOX mutations
often reveal older family members with same mutation who exhibit mild
skeletal features reminiscent of the Turner syndrome, such as
high-arched palate, short neck, abnormal auricular development, cubitus
valgus, genu valgum, short fourth metacarpals, and Madelung deformity."
}