Neural tube defects and the 13q deletion syndrome: evidence for a critical region in 13q33-34.

Neural tube defects (NTD) are common findings in the 13q deletion syndrome, but the relationship between the 13q- syndrome and NTDs is poorly understood. We present a child with a 13q deletion and lumbosacral myelomeningocele. This was a boy with microcephaly, telecanthus, minor facial anomalies, and ambiguous genitalia. Cytogenetic and fluorescence in situ hybridization analysis showed a de novo 46,XY,del(13)(q33.2-->qter) with no visible translocation. By using microsatellite markers, the deletion breakpoint was mapped to a 350-kb region between D13S274 and D13S1311 and was paternal in origin. An analysis of 13q deletions with NTDs, including the present case, suggests that a deletion in 13q33-34 is sufficient to cause an NTD. The deletions associated with NTDs are distal to and nonoverlapping with the previously defined critical region in 13q32 for the major malformation syndrome [Brown et al., 1999: Am J Hum Genet 57: 859-866]. Our analysis also suggests that one or more genes in 13q33-34 produces NTDs by haploinsufficiency.

Tumors and tumor-like lesions of the oral cavity and related structures in Israeli children.

The present study comprises a total of 966 biopsies of the oral cavity and related structures obtained from children aged < or =15 years and examined at the Division of Oral Pathology of The Hebrew University. These cases represent 7.15% of the total number of biopsies (13508) during a fifteen-year period (1978-1992). Seven hundred and seventy six (776) biopsies (80.3%) represented inflammatory processes, cysts, pulp pathology and congenital malformations. The remaining 190 biopsies (19.7%) comprised neoplastic and tumor-like lesions: 18 (9.5%) were benign odontogenic neoplasms, 77 (40.5%) were benign non-odontogenic neoplasms, 18 (9.5%) were malignant tumors and the remaining 77 cases (40.5%) were tumor-like lesions.

Myelomeningocele and Waardenburg syndrome (type 3) in patients with interstitial deletions of 2q35 and the PAX3 gene: possible digenic inheritance of a neural tube defect.

From a spina bifida clinic we have identified two patients with a syndrome of myelomeningocele and Waardenburg syndrome type 3 (WS3). The patients each possess a single, de novo, interstitial deletion of chromosome 2 (2q35-36.2), including the PAX3 gene. Deletion of PAX3 was confirmed by fluorescence in situ hybridization (FISH). Analysis with PAX3 and flanking microsatellites shows that the deleted interval of chromosome 2 is of paternal origin and is at least 2 and 6 cM in the two patients. Interstitial deletions in this region result in the Waardenburg syndrome (WS1), but have not been associated with neural tube defects (NTDs). Although other etiologies have not been formally excluded, these patients raise the possibility of a digenic etiology of their NTDs via a genetic interaction of the deleted PAX3 gene with a second unidentified locus.

Partial trisomy 14 (q23 leads to qter) via segregation of a 14/X translocation.

An infant with delayed development and multiple congenital anomalies was found to possess a duplication of 14q23 leads to qter. This imbalance arose through segregation of a maternal 14/X translocation, observed in only 28% of the mother's cells. Although the X-chromosome-derived portion of the translocation was late replicating in the proposita, the autosomal segment was not inactivated, leading to functional trisomy for distal 14q. Phenotypic comparison to cases with similar duplications does not allow the clinical description of a partial trisomy syndrome.

Translocations in Prader-Willi syndrome.

The Prader-Willi Syndrome (PWS) has frequently been associated with chromosomal anomalies involving the region 15q11-q12. The first case of this syndrome associated with a de novo translocation involving chromosomes 11 and 15 is reported. The breakpoints were identified as 11q25 and 15q11 or q12[45, XX,t(11;15)(q25;q11-12)], resulting in the deletion of 15pter leads to 15q11-q12. Previously reported cases of PWS associated with translocations are reviewed in relation to the "deletion hypothesis."

Duplication of 16p from insertion of 16p into 16q with subsequent duplication due to crossing over within the inserted segment.

Two members of a large family had a similar multiple congenital anomalies mental retardation (MCA/MR) syndrome and an identical aberration of chromosome 16. Their mothers, who are first cousins, had a different abnormality of one chromosome 16, which appeared to be an acrocentric. We interpret these findings as an insertion of a segment of 16p into 16q. following a three-break rearrangement and meiotic crossing over. The two abnormal children have a duplication of 16p11 leads to p13. The clinical manifestations of these patients differ from those of previously reported cases of dup(16p).

The identification of Y chromosome translocations following Distamycin A treatment.

Pretreatment of PHA-stimulated lymphocyte cultures from normal males with 100 micrograms/ml Distamycin A for the final 24 h of incubation led to a striking decondensation of the heterochromatic portion of the long arm of the Y chromosome. The despiralized region of Yq maintained its fluorescent properties in this altered morphologic state. Two cases of Y chromosome translocation (Y/22 and Y/X) were identified with this technique. A review of the literature revealed 62 similar cases in which the phenotypic-karyotypic correlations were instrumental in the prenatal counseling of the family with the Y/22 translocation.

Pseudomosaicism in prenatal diagnosis: two simultaneous, independent reciprocal translocations.

Cytogenetic evaluation of cultured amniotic fluid cells showed mosaicism of three karyotypes: 46,XY; 46,XY [t(13;17)(q13;q25]; and 46, XY [t(11;12)(p11;q13)]. Reanalysis of cells from the four original culture flasks harvested individually revealed that both translocations derived from the same flask. Repeat amniocentesis, as well as peripheral blood obtained postnatally from a phenotypically normal male infant, demonstrated only normal chromosomes (46,XY). This observation represents a case of pseudomosaicism containing two different reciprocal translocations.