Inverted duplication of chromosome 5p14p15.3 confirmed with in situ hybridization.

Duplication of the short arm of chromosome 5 [dup(5)(p13.1p15.3)] has been associated with craniofacial malformations, cardiac defects, renal and intestinal malformations, limb abnormalities, and mental retardation. We report a 2-year-old white girl with a de novo 46,XX,inv dup(5)(p14p15.3) chromosome constitution, who presented with motor and language delays, bilateral strabismus, small posteriorly angulated ears, a high-arched palate, mild hypotonia, and an atrial septal defect. A CT scan of the head was normal. In situ hybridization with a cosmid probe specific for sub-band 5p15.3 (Oncor, Inc., Gaithersburg, MD) was used to identify the origin and orientation of the extra material. The milder manifestations in our patient are consistent with the hypothesis that significant phenotypic effects are associated with duplication of material proximal to band 5p14. This study demonstrates the usefulness of in situ probes in identifying the origin and orientation of duplicated genetic material.

Interstitial deletion of chromosome 10, del(10) (q11.2q22.1) in a boy with developmental delay and multiple congenital anomalies.

We describe a 4-year-old boy with an interstitial deletion of the long arm of chromosome 10: del(10) (q11.2q22.1). Frontal bossing, hypertelorism, bright blue iris color, up-slanting palpebral fissures, a flat nasal bridge, a broad nose, apparently low-set ears, micrognathia, deep philtrum, and hypotonia were noted neonatally. A murmur was noted at age 5 1/2 months and surgical repair of subaortic stenosis was required at 4 years. At 4 years micrognathia was no longer evident, but the palate was high-arched. The pattern of abnormalities included postnatal-onset slow growth, short stature, mental retardation, and cardiac anomalies.

X-inactivation pattern in an Ullrich-Turner syndrome patient with a small ring X and normal intelligence.

In a description of 8 girls who had Ullrich-Turner syndrome (UTS) with a small r(X), mental retardation, and other unusual findings, it was hypothesized that the distinctive phenotype was associated with the loss of the X inactivation center from the r(X) and lack of genetic inactivation of the ring [Van Dyke et al., 1992]. Here, we present a 17-year-old young woman with 45,X/46,X,r(X)(?p11q13) mosaicism, Ullrich-Turner syndrome, and normal intelligence. In situ hybridization with the X-centromere DNA probe DXZ1 (Oncor, Inc., Gaithersburg, MD) was performed on previously G-banded slides, and the probe hybridized to the centromere regions of the normal X and the ring. The r(X) appears to be inactivated since a buccal smear demonstrated 5% Barr bodies. Furthermore, DAPI stain and FISH analysis with the X-centromere DNA probe DXZ1 was employed to distinguish the inactive X from the active X, and verified the presence of a sex chromatin mass in fibroblasts. These observations are consistent with the active-ring-X-and-mental-retardation hypothesis since the ring in this patient, although very small, appears to be normally inactivated and she has normal intelligence.

Replication banding and molecular studies of a mosaic, unbalanced dic(X;15)(Xpter-->Xq26.1::15p11-->15qter).

We present a patient with a chromosomal mosaicism involving the X chromosome. One cell line is 45,X and the other has a de novo paternally derived dicentric X;15 translocation. Her karyotype is therefore 45,X/45,X,dic(X;15)(Xpter-->Xq26.1::15p11-->15 qter) based on G-banding. The presence of 2 centromeres on the derivative X was confirmed by fluorescence in situ hybridization (FISH) and a deletion of Xq26.1-->qter was confirmed by polymerase chain reaction (PCR) using DXS52 and DXYS154. Replication banding studies indicate that the derivative X is late replicating. Based on these studies, it is unclear whether inactivation has spread to proximal 15q. The patient has a unique phenotype distinct from Ullrich-Turner or Prader-Willi syndromes, but includes ataxia and language delay which are commonly seen in Angelman syndrome. These findings are contrary to those anticipated since deficiency of paternal genes at 15q12 typically leads to Prader-Willi syndrome. Molecular analysis of PCR-based polymorphisms of chromosome 15 and X indicates that uniparental disomy is not present for the X chromosome or chromosome 15 in either cell line. It is hypothesized that her phenotype results from the interaction of the 2 abnormal genotypes. Each abnormality may be diluted by the mosaicism and, in the derivative X line, by the possible variation among cells of inactivation spreading to chromosome 15.