A Rare Combination of Functional Disomy Xp, Deletion Xq13.2-q28 Spanning the XIST Gene, and Duplication 3q25.33-q29 in a Female with der(X)t(X;3)(q13.2;q25.33)

Abstract

We report a 19-year-old female patient with a history of short stature, primary ovarian insufficiency, sensorineural hearing loss, sacral teratoma, neurogenic bladder, and intellectual disability with underlying mosaicism for der(X)t(X;3)(q13.2;q25.33), a ring X chromosome, and monosomy X. Derivative X chromosomes from unbalanced X-autosomal translocations are preferentially silenced by the gene (Xq13.2) located within the X-inactivation center. The unbalanced X-autosomal translocation in our case resulted in loss of the gene thus precluding the inactivation of the derivative X chromosome. As a result, clinical features of functional disomy Xp, Turner's syndrome, and duplication 3q syndrome were observed. Importantly, indications of the derivative X chromosome were revealed by microarray analysis following an initial diagnosis of Turner's syndrome made by conventional cytogenetic studies approximately 18 months earlier. This case demonstrates the importance of utilizing microarray analysis as a first-line test in patients with clinical features beyond the scope of a well-defined genetic syndrome.

Prenatal identification of partial 3q duplication syndrome

“…Similarly, Wilson et al described a patient with corneal opacities and extended optic nerves, as well as underdeveloped olfactory bulbs, while Preiksaitiene et al described a patient with optic nerve dysplasia [5, 12]. Preiksaitiene et al, based on tests carried out in a family with recurrent syndromic spina bifida due to a familial balanced chromosomal rearrangement, concluded that the spinal defect was caused by a duplication of the 3q21-qter region, and thus covered the proximal region of the chromosome [12, 13]. In the described foetus, a caudal agenesis and significant shortening the long bones of the limbs was observed.…”

Currarino syndrome: a comprehensive genetic review of a rare congenital disorder

“…So far however, other chromosomal or gene anomalies were identified in only five patients (see below). Here, a CS phenotype was either associated with partial trisomy of chromosomes 13q and 20p [ 72 ], a duplication 3q26.32-q27.2 [ 73 ], a duplication 3q26.31-q29 with deletion 9p24.3-9p23 [ 74 ], a functional disomy Xp with deletion Xq13.2-q28 and duplication 3q25.33-q29 [ 75 ], or excessive heterochromatin in chromosome 9 (9qh) [ 76 ].…”

“…Here, the duplicated region turned out to be larger, comprising 24.6 Mb from 3q26.31-q29, and the patient also carried a de novo 12.5 Mb terminal deletion from 9p24.3-9p23. Moreover, Peterson et al described a female with a combination of functional disomy Xp, deletion Xq13.2-q28 and duplication 3q25.33-q29 [ 75 ]. This patient presented with features of CS (sacral teratoma and neurogenic bladder) as well as primary ovarian insufficiency, sensorineural hearing loss and intellectual disability.…”