Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome

  title={Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome},
  author={Ercole Rao and Birgit Weiss and Maki Fukami and Andreas Rump and Beate Niesler and Annelyse Mertz and Koji Muroya and Gerhard Binder and Stefan Kirsch and M. Winkelmann and Gabriele Nordsiek and Udo E. Heinrich and Martijn H. Breuning and Michael B. Ranke and Andr{\'e} Rosenthal and Tsutomu Ogata and Gudrun A. Rappold},
  journal={Nature Genetics},
Growth retardation resulting in short stature is a major concern for parents and due to its great variety of causes, a complex diagnostic challenge for clinicians. A major locus involved in linear growth has been implicated within the pseudoautosomal region (PAR1) of the human sex chromosomes. We have determined an interval of 170 kb of DNA within PAR1 which was deleted in 36 individuals with short stature and different rearrangements on Xp22 or Yp11.3. This deletion was not detected in any of… 
Deletion of the pseudoautosomal region in a male with a unique Y;13 translocation and short stature.
It is concluded that haploinsufficiency for this gene is responsible for the growth failure in a 10-year-old boy with idiopathic short stature who was found to have a unique Y;13 translocation.
Short Stature Homeobox-Containing (SHOX) Gene Deficiency: Genetics and Growth Response to Growth Hormone Treatment in Comparison with Turner Syndrome
Recombinant human growth hormone (GH) was demonstrated to be effective in improving the growth of patients with isolated SHOX deficiency during a 2-year randomized, controlled clinical trial; the study demonstrated similar efficacy in patients with Leri–Weill and Turner syndromes.
SHOX: pseudoautosomal homeobox containing gene for short stature and dyschondrosteosis.
  • T. Ogata
  • Biology, Medicine
    Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
  • 1999
Trisomy of the short stature homeobox‐containing gene (SHOX), resulting from a duplication‐deletion of the X chromosome
The relationship between levels of SHOX expression and human stature is suggested to be more complex than envisaged previously, and the presence of normal stature in the patient rather than tall stature is likely to represent the natural variation seen in patients with transcription factor disorders.
Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature.
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.
Trisomy of the Short Stature Homeobox-Containing Gene (SHOX) due to Duplication/Deletion of the X Chomosome: Clinical Implications on the Stature
It is proposed that in some cases of trisomy for the SHOX gene, the effect of overdosage per se may affect the stature, even in patients with preserved ovarian function, and that estrogen deprivation may not always be a contributor for tall stature.
Unexpected Phenotype in a Boy with Trisomy of the SHOX Gene
The hypothesis is that this chromosome re-arrangement disrupts the regular interaction between the enhancer and promoter, resulting in a transcription block, thus producing a lack of gene activation, causing the clinical feature of short stature.
Molecular cytogenetic analysis of a Xp21.3‐pter deletion in a family with normal and short stature
Clinical manifestations and molecular cytogenetic analysis in a mother and three of her daughters with deletion Xp21, and the effects of growth hormone therapy on the affected children are reported.
Identification of short stature caused by SHOX defects and therapeutic effect of recombinant human growth hormone.
The data suggest that short stature due to SHOX deletions is not a rare entity and in cases of unexplained growth failure, especially if associated with any mild skeletal disproportions, genetic analysis of SHOX should be considered.
Submicroscopic Xpter deletion in a boy with growth and mental retardation caused by a familial t(X;14).
This case report illustrates that contiguous gene syndrome related to the Xpter region may have an atypical clinical presentation and the usefulness of combined clinical, biochemical, molecular, and fluorescence in situ hybridization analysis.


Short stature in a girl with a terminal Xp deletion distal to DXYS15: localisation of a growth gene(s) in the pseudoautosomal region.
It is proposed that a growth gene(s) is present in the distal part of the pseudoautosomal region of a Japanese girl with short stature and a rearranged X chromosome that remained below the 3rd centile growth curve for Japanese girls.
Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome.
It is demonstrated that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance and have implications for the genetic organization of this portion of the human X chromosome.
Proximal deletions of the long arm of the Y chromosome suggest a critical region associated with a specific subset of characteristic Turner stigmata.
Four patients with deletions of the long arm of their Y chromosome and presenting with azoospermia and with or without Turner stigmata are described and a region located in proximal interval 5 of the Y chromosome involved in skeletal development and growth is delimit.
Short stature in a girl with partial monosomy of the pseudoautosomal region distal to DXYS15: further evidence for the assignment of the critical region for a pseudoautosomal growth gene(s)
The results provide further support for the previously proposed hypothesis that the region between DXYS20 and DXYS15 is the critical region for a pseudoautosomal growth gene(s).
Uniparental disomy 7 in Silver-Russell syndrome and primordial growth retardation.
The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7 and suggest to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardation.
Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome.
The use of cDNA and genomic probes from the Xp22-pter region allowed us to identify 12 different deletion intervals and to confirm, and further refine, the chromosomal assignment of X-linked recessive chondrodysplasia punctata and Kallmann syndrome genes.
Deletions within the pseudoautosomal region help map three new markers and indicate a possible role of this region in linear growth.
The authors' data suggest that a locus affecting height maps in a region of about 1.5 Mbp, distal to the DXS406 locus and proximal to theDXS415 locus, a region which includes two CpG islands, and rule out an involvement of very distal sequences at the X/Y telomeres.
Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP
It is proposed that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.
Mild phenotypic effects of a de novo deletion Xpter-->Xp22.3 and duplication 3pter-->3p23.
The correlation of cytogenetic and molecular data suggest that the mild phenotype of the proposita is most likely due to preferential inactivation of the entire der(X), which seems to be of paternal origin.