A 3.2 Mb deletion on 18q12 in a patient with childhood autism and high-grade myopia.

Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with unknown aetiology. Even though ASDs are suggested to be among the most heritable complex disorders, only a few reproducible mutations leading to susceptibility for ASD have been identified. In an attempt to identify ASD susceptibility genes through chromosome rearrangements, we investigated a female patient with childhood autism and high-grade myopia, and an apparently balanced de novo translocation, t(5;18)(q34;q12.

Non-disjunction of chromosome 13.

We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors. The latter finding is unique among human autosomal trisomies, where maternal MI (trisomies 15, 16, 21, 22) or MII (trisomy 18) errors dominate.

Systematic re-examination of carriers of balanced reciprocal translocations: a strategy to search for candidate regions for common and complex diseases.

Balanced reciprocal translocations associated with genetic disorders have facilitated the identification of a variety of genes for early-onset monogenic disorders, but only rarely the genes associated with common and complex disorders. To assess the potential of chromosomal breakpoints associated with common/ complex disorders, we investigated the full spectrum of diseases in 731 carriers of balanced reciprocal translocations without known early-onset disorders in a nation-wide questionnaire-based re-examination. In 42 families, one of the breakpoints at the cytogenetic level concurred with known linkage data and/or the translocation co-segregated with the reported phenotype, for example, we found a significant linkage (lod score=2.

Segmental haplosufficiency: transmitted deletions of 2p12 include a pancreatic regeneration gene cluster and have no apparent phenotypic consequences.

Segmental aneuploidy usually has phenotypic consequences but unbalanced rearrangements without phenotypic consequences have also been reported. In particular, harmless deletions of G-dark bands 5p14 and 16q21 have each been found in more than one independent family. Here, we report two families that were ascertained at prenatal diagnosis and had similar overlapping deletions that removed most of the gene poor G-dark band 2p12.

Computer-assisted prenatal aneuploidy screening for chromosome 13, 18, 21, X and Y based on multiplex ligation-dependent probe amplification (MLPA).

In routine prenatal diagnostics we used a commercial multiplex ligation-dependent probe amplification (MLPA) kit for aneuploidy screening for chromosomes 13, 18, 21, X and Y. We present the results of 1593 consecutive prenatal samples analysed and diagnosed prior to knowledge of the G-banding analysis during 8-month routine use of computer-assisted MLPA aneuploidy screening. In total, 27 aneuploidies were detected.

An excess of chromosome 1 breakpoints in male infertility.

In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group.

Prospective study comparing HR-CGH and subtelomeric FISH for investigation of individuals with mental retardation and dysmorphic features and an update of a study using only HR-CGH.

In a prospective study 94 individuals with mental retardation (MR) and dysmorphic features with normal conventional karyotypes were investigated by both subtelomeric FISH and high resolution CGH (HR-CGH) in order to compare the potential of the two techniques in this application. A total of 9.6% abnormalities were found with HR-CGH and subtelomeric FISH, with HR-CGH detecting 8.

Cytogenetic investigation of testicular carcinoma in situ and early seminoma by high-resolution comparative genomic hybridization analysis of subpopulations flow sorted according to DNA content.

Interpretation of data from comparative genomic hybridization (CGH) analysis of testicular neoplasms located within normal parenchyma is complicated, because the results may be influenced by a heterogeneity of subpopulations with different chromosomal aberrations and ploidy. In this study, therefore, early stages of testicular germ cell neoplasia were cytogenetically analyzed after flow sorting of nuclei according to their DNA ploidy. DNA from subpopulations with different ploidy was globally amplified by means of degenerate oligonucleotide primed polymerase chain reaction, labeled with FITC-dCTP and -dUTP by nick translation, and analyzed with high resolution CGH.

High-resolution comparative genomic hybridization detects extra chromosome arm 12p material in most cases of carcinoma in situ adjacent to overt germ cell tumors, but not before the invasive tumor development.

High-resolution comparative genomic hybridization (HR-CGH) analysis was performed on DNA purified from laser-capture microdissected carcinoma in situ (CIS) cells from nine cases of CIS, either from tissue without any invasive tumor or from testicular parenchyma adjacent to seminoma, nonseminoma, or a combined germ cell tumor. Before CGH analysis, DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and directly labeled with a mixture of FITC-dUTP and FITC-dCTP. CGH analysis revealed extra chromosome arm 12p material in six out of seven cases with CIS adjacent to overt tumors, but only a diminutive gain of 12q was noted in one of the two cases of CIS without invasive elements.

High-resolution comparative genomic hybridisation yields a high detection rate of chromosomal aberrations in childhood acute lymphoblastic leukaemia.

Background: Cytogenetic aberrations are of prognostic significance in childhood acute lymphoblastic leukaemias and a high detection rate could improve the biological understanding and classification of these diseases.

Methods: Bone-marrow samples from 92 children with acute lymphoblastic leukaemia were studied by high-resolution comparative genomic hybridisation (HRCGH) using dynamic standard reference intervals that enhance both specificity and sensitivity in the detection of aberrations.

Results: In 80 patients (87%) HRCGH revealed a total of 405 aberrations, mostly whole chromosome gains (n = 265) and partial losses (n = 80).

Interstitial deletion of the short arm of chromosome 1: attempt to establish a clinical phenotype (46,XX,del (1)(p22p32)).

A girl with a de novo interstitial deletion of the short arm of chromosome 1 (46,XX,del (1)(p22p32) is described with moderate developmental delay and minor phenotypic abnormality. These clinical manifestations are compared to previously reported patients with interstitial deletion of chromosome 1, in an attempt to identify a clinical phenotype which seems quite different from the syndrome linked to more terminal deletion of chromosome 1p, and perhaps from more proximal 1p deletion phenotype.

[Use of molecular biological methods in invasive prenatal genetic diagnosis].

In the past, prenatal cytogenetic analysis was limited by answering times of one to three weeks and lack of exact diagnosis of some structural abnormalities. The number of prenatal analyses of monogenic diseases was small due to lack of knowledge of the gene and the mutation in question. The introduction of molecular biological techniques allows prenatal diagnosis of the most frequent trisomies within one to two days and exact diagnosis of almost all structural abnormalities.