SHOX in Short Stature Syndromes

Blaschke, R.; Rappold, Gudrun

doi:10.1159/000063458

Cited by 18 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These peculiar findings of SHOX gene deletions (number exceeding the number of points mutations, and type mainly interstitial) are largely supported by the special structural features and the high recombination frequency of the pseudoautosomal PAR1 region. 9 The three point mutations found in our families were all located in the homeodomain region of the SHOX gene; interestingly, the T497C transition coding for the Phe136Leu (fig 1) occurs in a highly conserved domain of the homeobox, similar to the missense mutation reported by Grigelioniene et al 6 in another conserved region, while the other missense mutation alters a residue (Arg153Leu) which is less evolutionarily preserved, but is also mutated in another LWD patient. 6 These residues do not appear to make direct contact with target DNA, but they are likely to be important for the stability of the homeodomain.…”

Section: Discussionsupporting

confidence: 75%

SHOX point mutations and deletions in Leri-Weill dyschondrosteosis

Falcinelli¹,

Calabrese

Chiarelli

et al. 2002

Journal of Medical Genetics

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 75%

SHOX point mutations and deletions in Leri-Weill dyschondrosteosis

Falcinelli¹,

Calabrese

Chiarelli

et al. 2002

Journal of Medical Genetics

View full text Add to dashboard Cite

“…The frequency and location of point mutations and small deletions/insertions of SHOX are shown at the bottom. The graphic is a compilation of resources taken from publications by Mangs et al [43] and Blaschke et al [44]. …”

Section: Shox Genementioning

confidence: 99%

Short Stature due to SHOX Deficiency: Genotype, Phenotype, and Therapy

2011

View full text Add to dashboard Cite

SHOX deficiency is a frequent cause of short stature. The short stature homeobox-containing gene resides in the telomeric PAR1 region on the short arm of both sex chromosomes and escapes X inactivation. For this review, abstracts of 207 publications presented by PubMed for the search term ‘SHOX’ were screened. Heterozygote SHOX mutations (80% deletions) were detected in 2–15% of individuals with formerly idiopathic short stature, in 50–90% of individuals with Leri-Weill dyschondrosteosis, and in almost 100% of girls with Turner syndrome. Mutational analysis is primarily performed by MLPA analysis followed by gene sequencing if necessary. SHOX is a nuclear protein that binds to DNA and acts as a transcriptional activator. Orthologs are present in many vertebrates but not in rodents. Gene expression starting as early as 33 days postconception in humans is predominant in the mid portion of the buds and in the first and second pharyngeal arches. In the growth plate, hypertrophic chondrocytes express SHOX where it seems to have antiproliferative potency. The penetrance of SHOX deficiency is high, but its clinical expression is very variable becoming more pronounced with age and being more severe in females. Growth failure starts early during the first years of life and the height deficit present at preschool age seems not to deteriorate further. The mean adult height is –2.2 SDS. Auxological analysis of the body proportions (mesomelia), the presence of minor abnormalities, and the search for subtle radiographic signs are important keys to the diagnosis which has to be confirmed by genetic analysis. The growth-promoting effect of GH therapy approved for individuals with SHOX mutations seems to be equal to the effect seen in Turner syndrome.

show abstract

“…Other commonly reported features include renal anomalies, cardiac defects and a number of distinctive phenotypic features, such as webbed neck, low posterior hairline and cubitus valgus. Although overall intelligence is usually reported as normal, a particular neurocognitive Turner profile of normally developed language abilities and impaired visual-spatial abilities is common [2]. …”

Section: Introductionmentioning

confidence: 99%

Tall Stature and Gonadal Dysgenesis in a Non-Mosaic Girl 45,X

Fernández

Pásaro²

2010

Horm Res Paediatr

View full text Add to dashboard Cite

Turner’s syndrome, also known as ‘monosomy X’, is a genetic disorder that occurs in 1/2,500 female births and is hypothesized to result from haploinsufficiency of certain genes expressed from both sex chromosomes that escape X inactivation. While the classic karyotype related to Turner’s syndrome is 45,X, the majority of those affected actually have a mosaic chromosomal complement, most often with a second normal cell line (46,XX). The resulting phenotype is variable and related to the underlying chromosomal pattern, but it is characterized by three cardinal features: short stature (around 100%), ovarian failure (>90%) and congenital lymphedema (>80%). In this paper we report a molecular and cytogenetic investigation of a 26-year-old female with non-mosaic 45,X karyotype, who has a stature of 170 cm without GH treatment, and whose only apparent Turner feature is gonadal dysgenesis. The only possible explanation for the absence of Turner phenotype is the hidden mosaicism combined with an untreated gonadal dysgenesis. Our results support the theory that significant ascertainment bias exists in our understanding of Turner’s syndrome.

show abstract

SHOX in Short Stature Syndromes

Cited by 18 publications

References 24 publications

SHOX point mutations and deletions in Leri-Weill dyschondrosteosis

SHOX point mutations and deletions in Leri-Weill dyschondrosteosis

Short Stature due to SHOX Deficiency: Genotype, Phenotype, and Therapy

Tall Stature and Gonadal Dysgenesis in a Non-Mosaic Girl 45,X

Contact Info

Product

Resources

About