Biomedical subjects

Elisena Morizio

Publications and source records attributed to Elisena Morizio.

7 recordsLinked to original sources

PubMed2006

Identification and characterization of different SHOX gene deletions in patients with Leri-Weill dyschondrosteosys by MLPA assay.

Deletions of the SHOX gene (Xp22-Yp11.3) are associated with Leri-Weill dyschondrosteosys (LWD) and idiopathic short stature. It has been estimated that SHOX deletions occur in 1,000-2,000 individuals in the total population, suggesting that this alteration should be investigated in all cases with unexplained short stature. SHOX deletions are currently investigated using fluorescence in situ hybridization (FISH) or molecular analysis of intragenic CA repeats. However, both techniques show some limitations. In the present study, the use of the multiple ligation probe amplification (MLPA) assay for the identification and characterization of SHOX deletions in 15 LWD patients, 3 of which carriers of chromosome abnormalities involving the SHOX gene, is reported. MLPA analysis demonstrated the heterozygous deletion of SHOX in seven patients (46.6%), disclosing the presence of two different proximal breakpoints. In patients with abnormal karyotype, MLPA analysis was able to identify the chromosomal rearrangement, showing, in addition to the SHOX deletions, the gain or loss of other genes mapped on the X and Y chromosomes. Since MLPA analysis can be carried out on a simple buccal swab, avoiding invasive peripheral blood collection, this technique represents a fast, simple and high throughput approach in the screening of SHOX deletions, able to provide more information as compared to FISH and microsatellite analysis.

Abnormalities, Multiple↗

PubMed2005

Lack of correlation between elevated maternal serum hCG during second-trimester biochemical screening and fetal congenital anomaly.

OBJECTIVE: Isolated elevations in midtrimester maternal serum human chorionic gonadotrophin concentrations (MShCG) have been reported to be associated with a substantially increased likelihood of fetal congenital malformations. The reported malformations included a wide range of organ systems, originating at different embryologic developmental stages. The purpose of our study was to determine the significance of an isolated elevated MShCG (>2.5 MoM) in midtrimester for the detection of fetal structural anomalies in a large population. METHODS: Among 10,144 women who underwent a biochemical triple screen at 15 to 18 weeks' gestation, 463 patients, who had an elevated MShCG, but normal alpha-fetoprotein (AFP) and unconjugated estriol (uE3) levels, were identified. Patients with an integrated calculated Down syndrome risk above 1:250 were excluded. Only nonsmokers, at ages <35 years, without a history of prior fetal anomalies were included. The control group consisted of 463 patients with normal serum analyte concentrations and Down syndrome risks below 1:250, who were matched for maternal age and date of biochemical screen. All patients underwent a detailed genetic sonogram in which an anatomic survey and multiple 'soft markers' for aneuploidy were looked for. Newborns were examined by a senior pediatrician trained in dysmorphology. RESULTS: MShCG levels were 3.18 +/- 0.72 versus 0.99 +/- 0.43 MoM (p < 0.0001) in study and control groups respectively. Sonography revealed 8 versus 6 cases of major congenital anomalies among the 463 patients of their respective groups, and 39 versus 36 sonographic 'soft markers' for aneuploidy. Fetal karyotyping and neonatal examination for dysmorphology revealed 6 chromosomal anomalies (4 Down syndrome; 2 Turner syndrome) among the 8 major malformations in the study group, but none in the controls (p < 0.0001). Three of the 39 fetuses with 'soft markers' and elevated MShCG were found to have trisomy 21. CONCLUSION: Isolated elevation of MShCG does not confer an increased risk of fetal congenital anomalies other than chromosomal abnormalities. However, elevated MShCG levels in combination with sonographic 'soft markers' for aneuploidy were associated with a high incidence of chromosomal anomalies, despite a normal biochemical triple screen risk estimate.

Adult↗

PubMed2005

Identification in chromosome 8q11 of a region of homology with the g1 amplicon of the Y chromosome and functional analysis of the BEYLA gene.

The male-specific region (MSY) of the Y chromosome contains genes involved mainly in male sex determination and in spermatogenesis. The majority of genes involved in male fertility are localized in multiple copies in the long arm of the Y chromosome, within specific regions defined as "ampliconic regions." It has been suggested that these genes derived from X-linked or autosomal ancestors during evolution, providing a benefit for male fertility when transposed onto the Y chromosome. So far, the autosomal origin has been demonstrated only for two MSY genes, DAZ and CDY. In the present study we report on the identification within chromosome 8q11.2 of a region homologous to the g amplicon, containing the VCY2 (approved gene symbol BPY2), TTTY4, and TTTY17 genes. A search for ancestor genes within the 8q11.2 region allowed us to identify a gene named BEYLA and to characterize the genomic organization and the expression patterns of this gene.

Animals↗

PubMed2004

Identification of 14 rare marker chromosomes and derivatives by spectral karyotyping in prenatal and postnatal diagnosis.

Extra structurally abnormal chromosomes (ESACs) and cryptic rearrangements are often associated with mental retardation and phenotypic abnormalities. In some cases their characterisation, using standard cytogenetic techniques and fluorescence in situ hybridization (FISH), is difficult and time consuming, where a fast and accurate identification is essential, especially when such chromosomal aberrations are found in prenatal diagnosis. A recent molecular technique, spectral karyotyping (SKY), based on the spectral signature of 24 chromosome-specific painting probes labelled with different combinations of five fluorochromes, allows the simultaneous visualisation of all human chromosomes in different colours. We used SKY analysis on 14 cases with rare ESACs or cryptic unbalanced rearrangements found at pre- or postnatal diagnosis. SKY analysis permitted the classification of chromosome rearrangements in all 14 cases analysed in combination with FISH analysis.

Chromosome Aberrations↗

PubMed2003

Chromosome 11 rearrangements and specific MLL amplification revealed by spectral karyotyping in a patient with refractory anaemia with excess of blasts (RAEB).

A patient with refractory anaemia with excess of blasts (RAEB) had a complex karyotype with multiple markers. Spectral karyotyping (SKY) showed rearrangements including three different der(11), containing a very high number of MLL gene copies, shown by fluorescence in situ hybridization (FISH) analysis. Fibre-FISH experiments disclosed the presence of chromatin fibres with multiple MLL copies with a head-to-tail pattern. Apparently, no other region flanking the MLL site was present in the three der(11). MLL amplification was confirmed by the reverse transcription polymerase chain reaction (RT-PCR). The patient died 6 months after diagnosis, supporting the severe prognosis of sole MLL amplification.

Aged↗

PubMed2002

C677T mutation in the 5,10-MTHFR gene and risk of Down syndrome in Italy.

The C677T polymorphism of the MTHFR gene has been associated to maternal risk of Down syndrome, due to the detection of an higher prevalence of the T allele among mothers of children with trisomy 21, compared to control mothers. In order to confirm this association, we studied the presence of the C677T in 64 mothers of Down syndrome children and 112 controls from central Italy. An higher incidence of the mutant T allele in controls (48.2%) than in Down syndrome children mothers (44%) was detected. These results do not support the presence of an increased risk of Down syndrome in mothers carriers of the T allele in the Italian population.

Down Syndrome↗

PubMed2002

A peptidase gene in chromosome 8q is disrupted by a balanced translocation in a duane syndrome patient.

PURPOSE: To identify the gene disrupted by a de novo reciprocal balanced translocation t(6;8)(q26;q13) in a patient with Duane retraction syndrome (DURS). The break point in chromosome arm 8q is positioned within the DURS1 critical region. METHODS: Fluorescence in situ hybridization (FISH) analysis using cosmid and BAC clones covering the DURS1 locus was performed to define the break point position and its relationship with expressed sequence tags (ESTs) in the region. Once the interrupted gene was identified, the full-length cDNA was sequenced and the genomic organization defined. Eighteen patients with sporadic DURS without cytogenetic abnormalities involving the DURS1 region were screened for point mutations in the candidate DURS1 gene. RESULTS: A carboxypeptidase gene (CPAH) was directly interrupted between the first and second exons in a patient with DURS who carried a de novo reciprocal balanced translocation t(6;8)(q26;q13) involving the DURS1 region on chromosome arm 8q13. The gene was transcribed in at least two alternative mRNA forms, with different start and stop codons. CONCLUSIONS: The CPAH gene was interrupted in a patient with DURS carrying a translocation break point in the DURS1 region on chromosome 8q13. CPAH is therefore a likely candidate for this abnormality, even if the possibility that other genes are involved, either by direct effects on transcription units present in the first CPAH intron or by position effects, cannot be ruled out. Functional studies of the influence of this gene on the morphogenesis of eye muscles and their innervation may clarify this question.

Adult↗