De novo subtelomeric deletion additional to an inherited apparently balanced reciprocal translocation.

OBJECTIVE: We describe the analysis of an apparently balanced inherited reciprocal translocation in a fetus presenting with multiple congenital abnormalities, characterize the structural chromosome rearrangement, and report an unexpected additional imbalance to the inherited rearrangement. METHODS: DNA microarray was used to screen for genomic imbalance in subtelomeric and interstitial critical regions. High-resolution comparative genomic hybridization was used to screen for genomic imbalance at a genome-wide level. Fluorescence in situ hybridization using whole-chromosome painting and specific probes was used to characterize the inherited translocation, and the size of the de novoadditional deletion. RESULTS: An unexpected additional deletion was found in 7qter on derivative 10 of the inherited maternal reciprocal translocation t(7;10)(q11.23; p14). CONCLUSIONS: We show the usefulness of genome-wide and specific molecular cytogenetic techniques to explore apparently balanced rearrangements.

Semilobar holoprosencephaly prenatal diagnosis: an unexpected complex rearrangement in a de novo apparently balanced reciprocal translocation on karyotype.

We report a semilobar holoprosencephaly (HPE) in a post-intracytoplasmic-sperm-injection pregnancy. It was suggested by ultrasonography (US), documented on karyotype, identified with magnetic resonance imaging (MRI), established after birth and confirmed on post-mortem autopsy. An amniocentesis revealed a de novo apparently balanced reciprocal translocation 46,XY, t(7;8) (q31.3;q12). Fluorescence in situ hybridization (FISH) identified a deletion in the region of the Sonic Hedgehog gene (SHH) on der(8); nevertheless, the subtelomeric regions for chromosomes 7 and 8 were present. The parents decided to continue the pregnancy; a boy was born and survived for 3 days. The brain autopsy confirmed the semilobar HPE previously noted on US and MRI. Further, band-specific FISH revealed, in addition to SHH deletion, the presence of an inversion in the 7q translocated material on der(8). The parents' karyotypes were normal. An unexpected complex rearrangement was present in a de novo apparently balanced reciprocal translocation in a semilobar HPE.

Chromosome segregation in an infertile man carrying a unique pericentric inversion, inv(21)(p12q22.3), analysed using fluorescence in situ hybridization on sperm nuclei: significance for clinical genetics. A case report.

We report the case of a 40-year-old patient referred to our centre after 3 years of infertility. Karyotyping with the aid of fluorescence in situ hybridization (FISH) analysis showed a unique pericentric inversion of chromosome 21:46,XY,inv(21)(p12q22.3). This type of intrachromosomal structural rearrangement can lead to chromosome imbalance in offspring by producing unbalanced gametes if an odd number of crossover events occur within the inverted segment. Therefore, partial trisomy/monosomy with clinical consequences can be observed in the progeny of carriers. Semen samples from the inversion carrier were analysed by FISH using a combination of probes [a subtelomeric 21q probe and a locus-specific Down's syndrome critical region (DSCR) probe] to evaluate the proportion of recombinant chromosomes. Sperm-FISH analysis of 3400 spermatozoa revealed a 67.4% rate of balanced chromosomes (normal or inverted). The frequencies of recombinant chromosomes with duplication of the long arm and deletion of the short arm, and vice versa, were 11.2 and 21.4%, respectively. The risk for the couple of conceiving a child with an unbalanced chromosome 21 is estimated to be around 32%. This case study shows the utility of sperm-FISH analysis in the genetic counselling of a pericentric inversion in a male carrier to assess the frequency of recombinant chromosomes and therefore evaluate the probability of having a normal conception.

Classical West "syndrome" phenotype with a subtelomeric 4p trisomy.

We report a girl with mild mental retardation with onset of infantile spasms at age of 9 months. Treatment with a short course of adrenocorticotropic hormone (ACTH) was successful. Initially, a diagnosis of idiopathic West syndrome, with good neurological outcome and disappearance of epilepsy after treatment, was made. Conventional karyotype was normal. Reinvestigations were done at age 8 years, because of a new pregnancy. Karyotyping of both parents was done because of mild dysmorphic features in the proband, and to eliminate other causes than early age epilepsy as the etiology of her mental retardation. Parental karyotypes showed a balanced paternal translocation (4p;17q) resulting in partial 4p trisomy, without significant 17q monosomy in the proband. Chromosomal abnormalities usually lead to a severe West syndrome with poor prognosis of neurological outcome (persistent severe epilepsy, mental retardation, and behavioral disturbances). The presence of an undetected cytogenetic anomaly in our proband with transient hypsarythmia is unusual and led us to propose systematic telomeric screening in apparently "idiopathic" West syndrome patients with mild mental retardation and subtle dysmorphic features.

Sex chromosome mosaicism in males carrying Y chromosome long arm deletions.

Microdeletions of the long arm of the Y chromosome (Yq) are a common cause of male infertility. Since large structural rearrangements of the Y chromosome are commonly associated with a 45,XO/46,XY chromosomal mosaicism, we studied whether submicroscopic Yq deletions could also be associated with the development of 45,XO cell lines. We studied blood samples from 14 infertile men carrying a Yq microdeletion as revealed by polymerase chain reaction (PCR). Patients were divided into two groups: group 1 (n = 6), in which karyotype analysis demonstrated a 45,X/46,XY mosaicism, and group 2 (n = 8) with apparently a normal 46,XY karyotype. 45,XO cells were identified by fluorescence in-situ hybridization (FISH) using X and Y centromeric probes. Lymphocytes from 11 fertile men were studied as controls. In addition, sperm cells were studied in three oligozoospermic patients in group 2. Our results showed that large and submicroscopic Yq deletions were associated with significantly increased percentages of 45,XO cells in lymphocytes and of sperm cells nullisomic for gonosomes, especially for the Y chromosome. Moreover, two isodicentric Y chromosomes, classified as normal by cytogenetic methods, were detected. Therefore, Yq microdeletions may be associated with Y chromosomal instability leading to the formation of 45,XO cell lines.

[Fetal cells in the maternal blood and prenatal diagnosis]. / Cellules foetales dans le sang maternel et diagnostic anténatal.

Fetal loss after amniocentesis or chorionic villus sampling is a limit to prenatal diagnosis practice and to its generalization. The existence of fetal cells in the blood of pregnant women is now well established. Recognizing these cells with specific antibodies and isolating them with fluorescent or magnetic systems are the subject of numerous studies. However, to date, neither the sensitivity nor the specificity of these methods are sufficient to allow a non invasive prenatal diagnosis.

Incidence of AZF (azoospermia factor) deletions and familial forms of infertility among patients requiring intracytoplasmic spermatozoa injection (ICSI).

PURPOSE: The aim of our study was to determine the incidence of AZF deletions and familial forms of infertility suggesting autosomal mutations among patients requiring intracytoplasmic sperm injection with ejaculated sperm. METHODS: Cases with obstructive pathologies were excluded; 81 patients were classified according to the numeration of spermatozoa. The distribution was as follows: 10 cases with normal numeration (greater than 20 million/ml) (group 1), 10 cases with between 10 and 20 million/ml (group 2), 6 cases with between 5 and 10 million/ml (group 3), 15 cases with between 1 and 5 million/ml (group 4), 29 cases with less than 1 million/ml (group 5), and 11 azoospermic patients (group 6). The infertility of 11 of the 81 patients might be explained by testicular ectopy. RESULTS: We found two deletions limited to the AZFc region among our 81 infertile patients--one deletion in group 5 and one deletion in group 4 (both groups of oligozoospermic patients)--and no deletion in the groups with normal or subnormal numerations. We found six familial forms of infertility. We did not find any AZF deletion, neither in these 6 patients nor in the 11 with testicular ectopy. The identification of these families of infertile men will allow research of autosomal genes involved in male infertilities. CONCLUSIONS: It is important to test deletions of the AZFc region for oligozoospermic patients, and familial forms of infertility do not seem to concern the same individuals.