Balkan Journal of Medical Genetics

Most isodicentric X chromosomes are formed by the fusion of the short arms of the two Xs and have their breakpoints at the very distal short arm, resulting in loss of very little Xp material [7]. They represent a special case of idic (X) chromosome translocations, arising by several mechanisms and usually showing instability. This explains the observed high frequency of mosaicism in patients with more than 3.5 Mb material between the centromeres [8].

As to the origin of idic (Xp) chromosomes, in a series of 14 cases studied by polymorphic restriction enzyme sites, the majority (9/14) were found to be maternal [9]. Most females who are described as having this X chromosome abnormality and a variable presence of a second 45,X cell line, tend to be short and display primary amenorrhea, but no other, or only a few symptoms of Ullrich-Turner’s syndrome.

We describe the genetic investigation of a short girl with the 45,X/46,X, idic(X)(qter->p12.3::p12.3->qter) mocaisism and haploinsufficiency of the SHOX gene in both cell lines detected in peripheral blood. According to our molecular findings, the breakpoints on the Xps must be distal to the DMD gene.

The loci tested were not completely informative, although they were considered to be rather polymorphic (heterozygosity up to 93%). Nevertheless, the overall data indicate that the abnormal idic (X) chromosome was most likely of maternal origin.

The phenotype of our patient primarily includes short stature and gonadal insufficiency with minor stigmata. Although the clinical confirmation of gonadal failure is lacking due to the young age of our patient, the very high levels of gonadotropin and especially of FSH, indicate a certain degree of gonadal insufficiency. The GH values on provocative testing indicate a partial GH deficiency. The GH levels are variable in Turner’s syndrome. Nevertheless, the short stature in this syndrome has not been attributed to GH insufficiency. Our proband?s stature most likely resulted from the monosomy of the region Xp21.3-> pter and the haploinsufficiency of the SHOX gene as determined by FISH analysis.

The present report indicates that in all cases with Xp or Yp rearrangements involving PAR1, FISH analysis should be applied for investigation of the presence of the SHOX gene and determination of the breakpoints [3-5,10,11]. Detailed descriptions of rearrangements in the SHOX locus, and the corresponding phenotype, will help to further define the SHOX function, and the clinical consequences of its molecular defects.