Browsing by Author "Nunes, Luis"
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- 16p13.11 microduplication: a case reportPublication . Marques, Bárbara; Ferreira, Cristina; Ventura, Catarina; Pedro, Sonia; Antunes, Diana; Nunes, Luis; Correia, HildebertoThe short arm of chromosome 16 is very rich in segmental duplications, predisposing this region of the genome to a number of recurrent rearrangements, namely deletions and duplications. Although it is already known that there is a strong association between 16p13.11 deletion and neuropsychiatric disorders, the clinical significance of its reciprocal duplication is not clearly defined yet. 16p13.11 microduplication that results of non-allelic homologous recombination is a very rare genetic alteration which can be associated with variable clinical features including behavioural abnormalities, developmental delay, congenital heart defects and skeletal anomalies. We report a 7-years-old boy with global developmental delay, speech absence, microcephaly, dysmorphic facial features and inexpressive facies. Microarray analysis revealed a 3.3Mb duplication comprising the 16p13.11- p12.3 region, which was confirmed by fluorescence in situ hybridization with a BAC clone for 16p13.11. Eight annotated genes are present in this region including NDE1, the candidate gene for neurological and behavioural phenotype. Although this microduplication has been found in the normal population, is significantly enriched in patients with autism, schizophrenia and cognitive impairment. Several case reports until now suggest that this genomic abnormality has incomplete penetrance and variable expressivity and can constitute a new syndrome. With this case we intend to contribute to expand the spectrum of clinical findings associated to this genomic abnormality and provide further knowledge of the pathogenic involvement of this duplication.
- 6q terminal deletion: a new contribution to genotype-phenotype correlationPublication . Simão, Laurentino; Marques, Bárbara; Sónia, Pedro; Antunes, Diana; Brito, Filomena; Silva, Neuza; Nunes, Luis; Correia, HildebertoDeletion of chromosome 6q is a relatively rare clinical entity associated to a considerable variability of the phenotypic spectrum. Mental retardation, facial dimorphisms, seizures, and brain abnormalities are typical features of this syndrome but until recently genotype-phenotype correlations have been scarce. We report a 15-year-old boy with slight developmental delay, intellectual disability, hypotonia, bilateral eye cataracts, mycrocephaly, agenesis of the corpus callosum, ventriculomegaly, paroxysmal attacks, kyphoscoliosis and trigonocephaly. Cytogenetic analysis revealed a de novo karyotype 46,XY,del(6)(q25.3). Microarrays genomic analysis with Cytoscan 750K allowed the refinement of the breakpoint region to 6q26q27, spanning approximately 7.76 Mb. The variation of the features attributed to 6q deletion syndrome is due primarily to differences in size and location of the segmental aneuploidy. Several studies suggest that deletions of 6q25 region can cause more severe anomalies that those including 6q26-27. Absence of IUGR, ear anomalies, ear loss, cleft palate, cardiac defects and genital hypoplasia in our patient are compatible with studies that generally correlate those features with deletions of 6q25 region. In addition, our patient presents retinal abnormalities, which has been associated to 6q26-q27 deletion. Some new candidate genes, localized at 6qter, have recently been described as being associated with some clinical features; an example is the candidate gene DLL1 and holoprosencephaly. Analysis of the breakpoints in most cases revealed a potential common breakpoint region at 8.0-9.0Mb from the chromosome 6q terminus where a fragile site exists (FRA6E). This suggests the breakage at the FRA6E may be the mechanism behind chromosome 6q subtelomeric deletions in some of the cases.Once the genotype-phenotype correlations have been scarce until now, with this study we aim to contribute to a better knowledge of the genotype-phenotype correlation of 6q terminal deletion and help to identify critical regions for several clinical features and developmental relevant genes.
- Prenatal Investigation of a Familial Partial Monosomy 10qPublication . Silva, Marisa; Marques, Bárbara; Brito, Filomena; Ferreira, Cristina; Furtado, José; Ventura, Catarina; Nunes, Luis; Kay, Teresa; Caetano, Paula; Correia, HildebertoObjective: To present the clinical, cytogenetic and molecular findings of a prenatal study of a familial partial monosomy 10q. Distal 10q deletions are rare and the majority are terminal deletions involving bands 10q25 and 10q26. Patients typically present with facial dysmorphism, postnatal growth retardation, developmental and mental retardation, genitourinary anomalies and digital anomalies. Methods: Conventional cytogenetic analysis in metaphases obtained by chorionic villi long term cultures, multiplex ligation dependent probe amplification (MLPA), fluorescent in situ hybridization (FISH), microarray analysis. Results: A 24-year-old gravida was referred for chorionic villus sampling at 12+6 weeks of gestation due to a previous child with facial dysmorphism, bilateral inguinal hernia, short stature and mild to moderate psychomotor delay of whom a microarray analysis was underway. His karyotype was normal but array-CGH analysis disclosed a 10q24.33-q25.1 interstitial deletion. The deletion encompasses 987Kb to 1,14Mb and includes 20 genes, in particular the COL17A gene. Fetal and parental karyotypes were normal. FISH analysis with a BAC clone located within the 10q region deleted in the phenotypically abnormal sibling showed normal results for both the mother and the fetus and a deletion in the apparently normal father. Conclusion: In this case chorionic villi analysis as well as the application of FISH with a specific and targeted BAC clone allowed a shorter turnaround time for the prenatal investigation of the chromosomal abnormality. The authors discuss the challenges of microarray analysis application in the prenatal setting namely in cases like the one presented here where there seems to be phenotypic variability.