Original ArticleThe Phenotype of Short Stature Homeobox Gene (SHOX) Deficiency in Childhood: Contrasting Children with Leri-Weill Dyschondrosteosis and Turner Syndrome
Section snippets
Methods
SHOX deletions were detected either by fluorescence in situ hybridization (FISH), as previously described,10 or by loss of heterozygosity of a polymorphic microsatellite marker (SHOX-CA) tightly linked to the SHOX locus.4
SHOX point mutations were detected by a commercial assay that uses denaturing high performance liquid chromatography to screen for heterozygosity (SHOX-DNA-Dx, Esoterix Endocrinology, Calabasas Hills, CA). Mutations were characterized by direct sequencing of genomic PCR
Molecular Analysis of SHOX Deletions and Mutations in the Clinical LWD Population
SHOX abnormalities present in the clinical population of subjects with LWD are listed in Table I. Complete gene deletion was detected by fluorescence in situ hybridization (FISH, Figure 1) in 29 subjects from 26 unrelated families. Eleven patients had karyotypic abnormalities that were the basis for ascertainment for this study. One subject (770) had a partial deletion of the SHOX locus, as evidenced by apparent inheritance from the mother of a null allele of a microsatellite marker (SHOX-CA)
Discussion
This study summarizes the genetic and physical findings from a group of 34 prepubertal children with LWD and confirmed SHOX gene deletion or mutation followed in a tertiary referral center. These results are based on a population of referred children subject to ascertainment bias. In addition, pretreatment data from a GH observational study were used to compare aspects of the phenotype of LWD females with those of another SHOX haploinsufficient population, females with TS. Other large studies
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2019, International Journal of PaleopathologyCitation Excerpt :It is important to note that the severity of this condition can vary widely between individuals, even in those from the same family, such that characteristics like short stature can manifest in diverse ways (Lemire and Wiebe, 2009; Schiller et al., 2000; Shears et al., 1998). LWD tends to be more severe in females compared to males (Child et al., 2015; Lichtenstein et al., 1980; Ross et al., 2005; Schiller et al., 2000; Shears et al., 1998). U36.Sh2.B10 displays many of the traits associated with LWD, including short stature, marked shortening of the forearms, Madelung’s deformity, mesomelia, and cubitus valgus.
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Supported in part by NIH grants NS42777 and NS35554 and Eli Lilly and Company.