J. O. Van Hemel

Molecular detection of a translocation (Y;11)(q11.2;q24) in a 45,X male with signs of Jacobsen syndrome

SummaryA 45,X karyotype was found in a boy with dysmorphic features, hypoglycaemia and pancytopenia. DNA analysis showed the presence of the Y-chromosomal DNA sequences SRY, ZFY, DYZ4, DYZ3 and DYS1. Using fluorescent in situ hybridization, we located DYZ4 and DYZ3 on chromosome llqter and concluded that a de novo translocation (Y;11)(q11.2;q24) with a deletion of 11q24→qter and a deletion of Yq11.2→Yqter were present; Jacobsen syndrome and azoospermia are associated with these deletions. Signs of Jacobsen syndrome were observed in the patient.

Recurrence of DiGeorge syndrome: prenatal detection by FISH of a molecular 22q11 deletion.

We report on a prenatal diagnosis by FISH of a familial 22q11 deletion associated with DiGeorge syndrome (DGS). The deletion was seen in the proband with symptoms of full DGS, in the physically normal father, and in a subsequent pregnancy. After birth this child showed hypocalcaemia, a T cell deficit, and a right sided aortic arch.

Ring chromosome 2: Clinical, chromosomal, and biochemical aspects

SummaryA new case of ring chromosome 2 is described and compared with the five cases hitherto reported. The clinical picture includes a severe pre- and postnatal growth failure, microcephaly, psychomotor retardation, and some minor dysmorphic features. Cytogenetic studies revealed a ring 2 structure and aneuploidy. Banding analysis failed to demonstrate a substantial loss of chromosomal material. Enzymologic studies revealed a decrease of red cell acid phosphatase activity suggesting the localization of its gene in the 2p25→2pter region.

De novo deletion (2) (p11.2p13): clinical, cytogenetic, and immunological data.

We report a case of a boy with a de novo interstitial deletion of chromosome (2) (p11.2p13). Clinical features included dysmorphism of the face, genital region, and limbs, psychomotor retardation, and vitiligo. A reduced ratio of immunoglobulin (Ig) light chain expression (kappa/lambda ratio: 0.7) was found, compatible with deletion of one Ig kappa allele on chromosome 2p12. The patient had no clinical or laboratory signs of immunodeficiency.

At least nine cases of trisomy 11q23-->qter in one generation as a result of familial t(11;13) translocation.

Carriers of balanced reciprocal translocations may have a (high) risk for producing liveborn children with an unbalanced karyotype. We report a large family in which a translocation between the long arm of chromosome 11 and the short arm of chromosome 13 is segregating in at least five generations. During the course of our study 15 carriers of the balanced translocation were identified and nine cases of partial trisomy of the long arm of chromosome 11 were detected during pre- and postnatal studies. Several of the patients were thoroughly clinically examined and compared with similar published cases.

DNA diagnosis of Prader-Willi and Angelman syndromes with the probe PW71 (D15S63)

Previously, 158 nuclear families with probands suspected of having either Prader Willi (PWS) or Angelman syndrome (AS) were analyzed with polymorphic DNA markers from the 15q11–13 region. These cases have been re-evaluated with the probe PW71 (D15S63), which detects parent-of-origin-specific alleles after digestion with a methylation-sensitive restriction enzyme (HpaII). Application of PW71 to DNA samples isolated from leucocytes, confirmed the deletions and uniparental disomies detected earlier by marker analysis, and resolved 50% of the previously uninformative (n=18) cases. PW71 and restriction fragment length polymorphism analysis indicated that, in all resolved cases, disomies of the 15q11–13 region were present. The use of PW71 increased the percentage of disomies detected in our PWS and AS patient groups. Almost 50% of our PWS patients and 17% of the AS patients showed a disomy of maternal or paternal origin, respectively. DNA of first trimester chorionic villi and of fibroblast cultures was not suitable for analysis with PW71 because of different methylation patterns. The application of PW71 is recommended for the diagnosis of the PWS and AS, with respect to DNA samples from blood.

Paracentric inversion inv(11) (q21q23) in the Netherlands

SummaryWe report the result of investigations from 20 families with 72 carriers of the paracentric inversion inv(11)(q21q23) in the Netherlands. There is no increase in the rate of spontaneous abortions among carriers of the inversion or their partners. Also, so far, there are no children with recombinant chromosomes arising from the inversion. It is doubtful whether prenatal diagnosis would be helpful to carriers of this inversion. The results of the genealogy study and geographical distribution are discussed; it is suggested that all the families have arisen from a single mutation.