Microduplication 3p26.3p24.3 and 4q34.3q35.2 Microdeletion Identified in a Patient with Developmental Delay Associated with Brain Malformation.

Microdeletions and microduplications are involved in many of prenatal and postnatal cases of multiple congenital malformations (MCM), developmental delay/intellectual disability (DD/ID), and autism spectrum disorders (ASD). Molecular karyotyping analysis (MCA), performed by DNA microarray technology, is a valuable method used to elucidate the ethology of these clinical expressions, essentially contributing to the diagnosis of rare genetic diseases produced by DNA copy number variations (CNVs). MCA is frequently used as the first-tier cytogenetic diagnostic test for patients with MCM, DD/ID, or ASD due to its much higher resolution (≥10×) for detecting microdeletions and microduplications than classic cytogenetic analysis by G-banded karyotyping. Therefore, MCA can detect about 10% pathogenic genomic imbalances more than G-banded karyotyping alone. In addition, MCA using the Single Nucleotide Polymorphism-array (SNP-array) method also allows highlighting the regions of loss of heterozygosity and uniparental disomy, which are the basis of some genetic syndromes. We presented a case of a five-year-old patient, with global development delay, bilateral fronto-parietal lysencephaly, and pachygyria, for which MCA through SNP-Array led to the detection of the genetic changes, such as 3p26.3p24.3 microduplication and 4q34.3q35.2 microdeletion, which were the basis of the patient's phenotype and to the precise establishment of the diagnosis.

A Case of Inherited t(4;10)(q26;q26.2) Chromosomal Translocation Elucidated by Multiple Chromosomal and Molecular Analyses. Case Report and Review of the Literature.

We present a complex chromosomal anomaly identified using cytogenetic and molecular methods. The child was diagnosed during the neonatal period with a multiple congenital anomalies syndrome characterized by: flattened occipital region; slight turricephaly; tall and broad forehead; hypertelorism; deep-set eyes; down slanting and short palpebral fissures; epicanthic folds; prominent nose with wide root and bulbous tip; microstomia; micro-retrognathia, large, short philtrum with prominent reliefs; low set, prominent ears; and congenital heart disease. The GTG banding karyotype showed a 46,XY,der(10)(10pter→10q26.2::4q26→4qter) chromosomal formula and his mother presented an apparently balanced reciprocal translocation: 46,XX,t(4;10)(q26;q26.2). The chromosomal anomalies of the child were confirmed by MLPA, and supplementary investigation discovered a quadruplication of the 4q35.2 region. The mother has a triplication of the same chromosomal fragment (4q35.2). Using array-CGH, we described the anomalies completely. Thus, the boy has a 71,057 kb triplication of the 4q26-q35.2 region, a 562 kb microdeletion in the 10q26.3 region, and a 795 kb quadruplication of the 4q35.2 region, while the mother presents a 795 kb triplication of the 4q35.2 region. Analyzing these data, we consider that the boy's phenotype is influenced only by the 4q partial trisomy. We compare our case with similar cases, and we review the literature data.

Critical steps in tissue processing in histopathology.

Histopathological diagnosis using Formalin-Fixed Paraffin Embedded (FFPE) tissues is essential for the prognostic and therapeutic management of cancer patients. Pathologists are being confronted with increasing demands, from both clinicians and patients, to provide immunophenotypic and gene expression data from FFPE tissues to allow the planning of personalized therapeutic regimens. Recent improvements in the protocols for pre-analysis processing of pathological tissues aim to better preserve cellular details and to conserve antigens and nucleic acid sequences. These developments have been recently patented. The international protocol for the transporting of surgical specimens from the surgical theatre to the pathology department is to immerse the specimen in formalin. The alternative method of sealing the specimens into bags under a vacuum and then cooling is a well-accepted and environmentally safe procedure that overcomes the many drawbacks linked to transfer in formalin. Importantly, RNA is notoriously poorly preserved in FFPE tissue. Due to this, successful procedures for the extraction of genetic information from archival tissues have been the object of several studies and patents. Novel molecular approaches for RT-qPCR and gene array analysis on FFPE tissues are presented here. Moreover, a major advance is reported in this study, the observation that tissue fixation in cold conditions allows a much better preservation of nucleic acid sequences.

Oculocutaneous albinism associated with multiple malformations and psychomotor retardation.

We present a case of oculocutaneous albinism in a child associating multiple malformations (preaxial polydactyly, small penis, cardiac malformation) and psychomotor retardation. To our knowledge, this association has not been previously described.