Virilization of the external genitalia and severe mental retardation in a girl with an unbalanced translocation 1;18.

A female infant with dysmorphic facial features, psychomotor retardation, and clitoris hypertrophy is described. Molecular cytogenetic analyses revealed a de novo unbalanced translocation, causing partial monosomy 1p36 and partial trisomy 18q22. Monosomy 1p was confirmed by FISH, and trisomy of the distal part of chromosome 18q was demonstrated by microFISH. Gene copy number changes in these chromosomal regions were determined by array-CGH. The absence of a number of facial dysmorphic signs, and the presence of clitoris hypertrophy indicate that the combination of a del(1p36->pter) with a dup(18q22->qter) may lead to a unique phenotypic constellation. The findings at birth and at age 12 years in our patient are compared with genotype-phenotype correlations discussed in the literature.

Supernumerary ring chromosome 7 mosaicism: case report, investigation of the gene content, and delineation of the phenotype.

We report a girl with severe retardation of expressive speech development carrying a small, supernumerary ring chromosome derived from the proximal region of the long arm of chromosome 7. The r(7) chromosome is present in 50% of lymphocytes. We also review the six additional cases with a supernumerary r(7) chromosome reported in the literature. Among these patients, a severe retardation of productive language capabilities is seen as a shared clinical feature, irrespective of the degree of mosaicism as detected in blood. The dysmorphisms in these patients are minor and no shared congenital abnormalities seen. We, therefore, recommend chromosomal investigations in children with unexplained, disproportionately retarded expressive speech performance. Because speech and language acquisition are subject to genetic influences, we investigated whether there are genes on the r(7) chromosome that may affect brain development or function in a dosage-dependent manner. We found that both in our patient and in four patients described by others, the supernumerary r(7) chromosome contains the region from the centromere up to marker D7S613 located at 7q11.23. We speculate that the effects on speech acquisition are mediated by the supernumerary copies of the STX1A and LIMK1 genes, which are both located in this region and known to suppress neurite growth when overexpressed in vitro.

Prenatal detection of complex chromosomal aberrations using advanced molecular cytogenetic techniques.

OBJECTIVE: This study aimed to identify a marker chromosome and characterize the short arm of a derivative chromosome 5 in a foetus with the following karyotype: mos 47,XX,del(5)(p?),+i(5)(p10)[50]/48,XX,del(5)(p?),+i(5)(p10),+mar[25]. METHOD: Amniocentesis was performed in the 26th week of pregnancy because of ultrasound abnormalities (polyhydramnion and decreased amount of gastric filling). All classic banding techniques were performed. FISH and microdissection combined with reverse painting were used to reveal the exact origin of the marker and any extra material on the deleted chromosome 5p. The parents decided to continue the pregnancy and we compared the clinical features of the child born in week 34 with data from the literature on trisomy 5p. The possible contribution of trisomy of the centromeric region of chromosome 8 and trisomy 8p23.3-->8pter to this clinical picture was evaluated. RESULTS: GTG banding showed one normal and two aberrant chromosomes 5 [del(5)(p?) and i(5)(p10)] in all the cells examined. Furthermore, a supernumerary marker chromosome was present in approximately 30% of the cells. The marker was CBG positive and positive with the pancentromere probe, but dystamicinA/DAPI negative. It did not contain NOR-positive satellites. FISH proved this marker to be derived from the centromeric region of chromosome 8. MicroFISH disclosed the aberrant chromosome 5 as der(5)t(5;8)(p10;p23.3). The parent's karyotypes were normal. The baby showed the characteristic features of trisomy 5p syndrome. She died at the age of 15 days after cardiorespiratory arrest. CONCLUSION: The karyotype was interpreted as mos 47,XX,add(5)(p10).rev ish der(5)t(5;8)(p10;p23.3),+i(5)(p10) (WCP5+,D5S23+)[50]/48,XX,add(5)(p10).rev ish der(5)t(5;8)(p10;p23.3),+i(5)(p10)(WCP5+,D5S23+),+mar.ish 8(p10q10)(D8Z2+,WCP8-)[25]. Therefore, the baby had complete trisomy 5p, with trisomy of the distal part of 8p and of the centromeric region of chromosome 8. The clinical significance of de novo marker chromosomes is a major problem in prenatal counselling. Molecular cytogenetic tools such as FISH and microFISH are indispensable for characterizing markers and determining the breakpoints more precisely in deleted chromosomes.

Characterization of partial trisomy 9p due to insertional translocation by chromosomal (micro)FISH.

We describe a family with an insertion 12;9 translocation occurring in a balanced form in a mother and two sons, but in an unbalanced form in the proband, resulting in trisomy of chromosome region 9p22-->9p24. The proband manifests typical features of trisomy 9p; the clinical signs were mental and growth retardation, microcephaly, epicanthus, low-set ears, micrognathia, clinodactyly and hypoplastic phalanges of the fifth fingers, hypoplasia or absence of toenails, and extremely small genitals. The GTG-banded findings were confirmed using (micro)FISH. Intriguingly, the mother and the two carrier sons exhibited major learning difficulties that were not present in the non-carrier sister of the mother: this may be due to a gene disruption or induction of abnormal expression. Dysmorphic features were not present in the three carriers. We compare our clinical and cytogenetic findings with other cases of partial trisomy 9p reported in the literature.

Latent X-ray damage in the rat sciatic nerve results in delay in functional recovery after a heat treatment.

The influence of X-irradiation on the sensitivity of the rat sciatic nerve to local hyperthermia was investigated. A 10 or 20 mm long segment of the nerve was irradiated intraoperatively using 50 kV X-rays. Hyperthermia (30 min at 45 degrees C), was applied to the irradiated part (over a length of 5 mm) of the nerve using a brass thermode. Functional damage to the nerve was assessed using the toe-spreading test, which mainly assesses the motor function of the sciatic nerve. Radiation alone (doses up to 70 Gy) did not lead to detectable damage for at least 90 weeks. Hyperthermia alone (30 min at 45 degrees C) resulted in complete loss of motor function. This function loss was transient and complete recovery took place in about 4 weeks. Recovery time was scored as the number of days between hyperthermia and the day on which 50% of the motor function had returned. Irradiation (35 Gy) of a nerve segment, which included the heated part, resulted in a delayed recovery from the heat treatment compared to controls (heat only). The time interval and sequence between irradiation and hyperthermia hardly influenced the recovery delay. The size of the irradiated nerve segment did influence the recovery delay. Irradiation of a 20 mm nerve segment led to longer recovery delays than irradiation of a 10 mm segment (a delay of 5-10 days and 1-5 days respectively). A dose-response relation for the irradiation-induced delay in recovery was observed when a large segment (20 mm) of the nerve was irradiated immediately after heat with a dose ranging from 5 to 40 Gy. The delay in heat recovery was dose-dependent below 20 Gy, but after radiation doses above 20 Gy the recovery delay remained almost constant.