Herman Van den Berghe

Genetic modelling of dizygotic twinning in pedigrees of spontaneous dizygotic twins

The inheritance of spontaneous dizygotic (DZ) twinning was investigated in 1,422 three-generation pedigrees ascertained through mothers of spontaneous DZ proband twins. DZ twinning was modelled as a trait expressed only in women. The penetrance was modelled first as a parity independent and secondly as parity dependent. The observed frequencies of maternal and paternal grandmothers with DZ twins differed significantly from the expectations under an X-linked mode of inheritance. Complex segregation analysis showed that the parity-independent phenotype of having DZ twins was consistent with an autosomal monogenic dominant model, with a gene frequency of 0.035 and a female-specific lifetime penetrance of 0.10. Recessive, polygenic, and sporadic models were rejected. The autosomal dominant model revealed a strong robustness against a changing population prevalence and the loss of information due to the presence of same-sexed twin pairs of unknown zygosity. When DZ twinning was modelled as a parity dependent trait, the data were compatible with an autosomal dominant model with a gene frequency of 0.306 and a penetrance of 0.03 per birth for female gene carriers.

The Wiedemann-Rautenstrauch or neonatal progeroid syndrome

A 4-year-old girl is reported with a neonatally apparent progeroid syndrome. Parental consanguinity indicates autosomal recessive inheritance. Psychomotor development and physical growth are severely deficient. Mainly characterized by congenital absence of subcutaneous fat tissue, this child is very similar to four patients reported earlier and recognized as representing a newly delineated clinical entity, called here the Wiedemann-Rautenstrauch or neonatal progeroid syndrome.

Duplication of chromosome segment 12q15‐24 is associated with atypical lipomatous tumors. A report of the CHAMP collaborative study group

Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12q13‐15, and atypical lipomatous tumors (ALT) by supernumerary ring chromosomes or giant markers known to contain amplified 12q sequences. In a series of 228 cytogenetically analyzed and histopathologically reexamined ordinary lipomas and ALT, 10 tumors showed unbalanced chromosome‐12 aberrations. All 4 tumors with loss of segments from 12q were classified as ordinary lipomas, whereas 5 of the 6 tumors showing gain of 12q material were diagnosed as ALT. One or three extra copies of 12q15‐q24 were present in all 5 ATL. We conclude that duplication of 12q sequences may be a sufficient level of amplification for development of the microscopic appearance that characterizes ALT.

Identification of an enriched CD4+ CD8α++ Cd8β+ T-cell subset among tumor-infiltrating lymphocytes in human renal cell carcinoma

Three‐color immunofluorescence flow‐cytometric analysis of freshly isolated tumor‐infiltrating lymphocytes (TIL) from patients with primary renal cell carcinoma (RCC) revealed a unique, not previously described TIL subset with a CD3+ CD4+ CD8α++ CD8β+ phenotype. This subset represented at least 5% of CD3+ TIL in 15 of 21 patients with clear cell RCC, whereas it was not or only marginally represented in patients with papillary RCC or sarcomatoid RCC. In one‐third of the patients with clear cell RCC, more than 20% of CD3+ TIL and in one patient more than half of the CD3+ TIL displayed this phenotype. The occurrence of this subset was not associated with pathological stage, tumor diameter, nuclear grade, cytogenetic abnormalities or vascular invasion in this patient cohort. When present, the CD3+ CD8α++ CD8β+ subset was detected in similar proportions in tumor tissue and tumor capsula, and it was also detected in adjacent non‐tumoral renal tissue, albeit in much lower proportions. Despite strong cell surface expression of various activation markers (CD69, CD54 and HLA‐DR), CD3+ CD4+ CD8α++ anti‐CD3‐redirected cytotoxicity assay. In contrast with CD3+ CD4+ CD8− cells from the same tumor sample, they were markedly deficient in IL‐2Rα up‐regulation following anti‐CD3 triggering. The possibility that these cells represent either anergic cells or a highly specialized effector population with a discrete, as yet undescribed function is discussed. Int. J. Cancer 71:178–182, 1997.

5q — syndrome in a child

A boy aged 8 years, 10 months presented with refractory anemia. Bone marrow investigation revealed monolobular megakaryocytes. Cytogenetic analysis showed a clonal abnormality: 46, XY, del(5)(q14q32). This is the youngest individual ever reported with this disorder. A year after diagnosis, while on treatment with human recombinant erythropoietin, the bone marrow showed an excess of blasts. No bone marrow donor could be found. Transformation to acute myelomonocytic leukemia occurred 3 months later. In spite of intensive chemotherapy, the child died of progressive disease with massive splenomegaly and jaundice. The case illustrates that the 5q- syndrome can occur de novo in children. The outcome in this child was poor, which may reflect a difference from the adult 5q- syndrome or may possibly be related to the erythropoietin the child received.