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1.
Clin Genet ; 105(3): 313-316, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37990933

RESUMO

We report the case of a 12-year-old girl and her father who both had marked postnatal tall stature, camptodactyly and clinodactyly, scoliosis and juvenile-onset hearing loss. The CATSHL (CAmptodactyly - Tall stature - Scoliosis - Hearing Loss syndrome) syndrome was suspected, and molecular analysis revealed a hitherto unreported, monoallelic variant c.1861C>T (p.Arg621Cys) in FGFR3. This variant affects the same residue, but is different than, the variant p.Arg621His reported in the two families with dominant CATSHL described so far. Interestingly, peg-shaped incisors were observed in the proband, a feature never reported in CATSHL but typical of another FGFR3-related condition, LADD (Lacrimo - Auricolo - Dento - Digital) syndrome. The FGFR3 p.Arg621Cys variant seems to be a newly identified cause of CATSHL syndrome with some phenotypic overlap with the LADD syndrome.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Surdez , Deformidades Congênitas da Mão , Perda Auditiva , Doenças do Aparelho Lacrimal , Deformidades Congênitas dos Membros , Escoliose , Sindactilia , Anormalidades Dentárias , Feminino , Humanos , Criança , Escoliose/genética , Perda Auditiva/genética , Síndrome
2.
Prenat Diagn ; 42(13): 1575-1586, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36403097

RESUMO

OBJECTIVES: To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories. METHODS: Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non-invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed. RESULTS: Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs. PPVs for T21, T18, and T13 were significantly higher when diagnostic confirmation was carried out on chorionic villi (97.5%) compared to amniotic fluid (89.5%) (p < 0.001). In 19/139 (13.9%), of no result cases, a cytogenetic abnormality was detected. Follow-up genetic testing provided explanations for 3/6 cases with a fetal sex discordancy between NIPT and ultrasound. CONCLUSIONS: NIPT PPVs differ across the conditions screened and the tissues studied in diagnostic testing. This variability, issues associated with fetal sex discordancy, and no results, illustrate the importance of pre- and post-test counselling.


Assuntos
Ácidos Nucleicos Livres , Feminino , Humanos , Gravidez , Análise Citogenética , Valor Preditivo dos Testes , Diagnóstico Pré-Natal/métodos , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Itália
3.
Int J Mol Sci ; 23(6)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35328767

RESUMO

Improvements in microarray-based comparative genomic hybridization technology have allowed for high-resolution detection of genome wide copy number alterations, leading to a better definition of rearrangements and supporting the study of pathogenesis mechanisms. In this study, we focused our attention on chromosome 8p. We report 12 cases of 8p rearrangements, analyzed by molecular karyotype, evidencing a continuum of fragility that involves the entire short arm. The breakpoints seem more concentrated in three intervals: one at the telomeric end, the others at 8p23.1, close to the beta-defensin gene cluster and olfactory receptor low-copy repeats. Hypothetical mechanisms for all cases are described. Our data extend the cohort of published patients with 8p aberrations and highlight the need to pay special attention to these sequences due to the risk of formation of new chromosomal aberrations with pathological effects.


Assuntos
Aberrações Cromossômicas , Genoma , Hibridização Genômica Comparativa , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente
4.
Int J Mol Sci ; 23(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35682590

RESUMO

KBG syndrome (KBGS) is a neurodevelopmental disorder caused by the Ankyrin Repeat Domain 11 (ANKRD11) haploinsufficiency. Here, we report the molecular investigations performed on a cohort of 33 individuals with KBGS clinical suspicion. By using a multi-testing genomic approach, including gene sequencing, Chromosome Microarray Analysis (CMA), and RT-qPCR gene expression assay, we searched for pathogenic alterations in ANKRD11. A molecular diagnosis was obtained in 22 out of 33 patients (67%). ANKRD11 sequencing disclosed pathogenic or likely pathogenic variants in 18 out of 33 patients. CMA identified one full and one terminal ANKRD11 pathogenic deletions, and one partial duplication and one intronic microdeletion, with both possibly being pathogenic. The pathogenic effect was established by RT-qPCR, which confirmed ANKRD11 haploinsufficiency only for the three deletions. Moreover, RT-qPCR applied to six molecularly unsolved KBGS patients identified gene downregulation in a clinically typical patient with previous negative tests, and further molecular investigations revealed a cryptic deletion involving the gene promoter. In conclusion, ANKRD11 pathogenic variants could also involve the regulatory regions of the gene. Moreover, the application of a multi-test approach along with the innovative use of RT-qPCR improved the diagnostic yield in KBGS suspected patients.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Deficiência Intelectual , Anormalidades Dentárias , Anormalidades Múltiplas/genética , Deleção Cromossômica , Fácies , Humanos , Deficiência Intelectual/genética , Fenótipo , Proteínas Repressoras/genética , Anormalidades Dentárias/diagnóstico , Anormalidades Dentárias/genética , Fatores de Transcrição/genética
5.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073228

RESUMO

The presence of thousands of repetitive sequences makes the centromere a fragile region subject to breakage. In this study we collected 31 cases of rearrangements of chromosome 18, of which 16 involved an acrocentric chromosome, during genetic screening done in three centers. We noticed a significant enrichment of reciprocal translocations between the centromere of chromosome 18 and the centromeric or pericentromeric regions of the acrocentrics. We describe five cases with translocation between chromosome 18 and an acrocentric chromosome, and one case involving the common telomere regions of chromosomes 18p and 22p. In addition, we bring evidence to support the hypothesis that chromosome 18 preferentially recombines with acrocentrics: (i) the presence on 18p11.21 of segmental duplications highly homologous to acrocentrics, that can justify a NAHR mechanism; (ii) the observation by 2D-FISH of the behavior of the centromeric regions of 18 respect to the centromeric regions of acrocentrics in the nuclei of normal subjects; (iii) the contact analysis among these regions on published Hi-C data from the human lymphoblastoid cell line (GM12878).


Assuntos
Cromossomos Humanos Par 18/genética , Translocação Genética , Adulto , Linhagem Celular Tumoral , Feminino , Humanos , Lactente , Masculino , Gravidez
6.
Cytogenet Genome Res ; 160(2): 80-84, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32018271

RESUMO

Unbalanced X;autosome translocations are a rare occurrence with a wide variability in clinical presentation in which the X chromosome unbalance is usually mitigated by a favorable X inactivation pattern. In most cases, this compensation mechanism is incomplete, and the patients show a syndromic clinical presentation. We report the case of a family with 4 women, of 3 different generations, carrying an unbalanced X;7 translocation with a derivative X;7 chromosome and showing a skewed X inactivation pattern with a preferential activation of the normal X. None of the carriers show intellectual disability, and all of them have a very mild clinical presentation mainly characterized by gynecological/hormonal issues and autoimmune disorders. We underline the necessity of family testing for a correct genetic consultation, especially in the field of prenatal diagnosis. We indeed discuss the fact that X;autosome translocations may lead to self-immunization, as skewed X chromosome inactivation has already been proved to be related to autoimmune disorders.


Assuntos
Doenças Autoimunes/genética , Transtornos Cromossômicos/genética , Cromossomos Humanos X/genética , Translocação Genética , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Linhagem , Fenótipo , Gravidez , Inativação do Cromossomo X
7.
Int J Mol Sci ; 21(10)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32413994

RESUMO

Satellited non-acrocentric autosomal chromosomes (ps-qs-chromosomes) are the result of an interchange between sub- or telomeric regions of autosomes and the p arm of acrocentrics. The sequence homology at the rearrangement breakpoints appears to be, among others, the most frequent mechanism generating these variant chromosomes. The unbalanced carriers of this type of translocation may or may not display phenotypic abnormalities. With the aim to understand the causative mechanism, we revised all the ps-qs-chromosomes identified in five medical genetics laboratories, which used the same procedures for karyotype analysis, reporting 24 unrelated cases involving eight chromosomes. In conclusion, we observed three different scenarios: true translocation, benign variant and complex rearrangement. The detection of translocation partners is essential to evaluate possible euchromatic unbalances and to infer their effect on phenotype. Moreover, we emphasize the importance to perform both, molecular and conventional cytogenetics methods, to better understand the behavior of our genome.


Assuntos
Aberrações Cromossômicas , Cromossomos/genética , DNA Satélite/genética , Translocação Genética , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Cariotipagem
8.
Int J Mol Sci ; 20(5)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30836598

RESUMO

Chromosome 16 is one of the most gene-rich chromosomes of our genome, and 10% of its sequence consists of segmental duplications, which give instability and predisposition to rearrangement by the recurrent mechanism of non-allelic homologous recombination. Microarray technologies have allowed for the analysis of copy number variations (CNVs) that can contribute to the risk of developing complex diseases. By array comparative genomic hybridization (CGH) screening of 1476 patients, we detected 27 cases with CNVs on chromosome 16. We identified four smallest regions of overlapping (SROs): one at 16p13.11 was found in seven patients; one at 16p12.2 was found in four patients; two close SROs at 16p11.2 were found in twelve patients; finally, six patients were found with atypical rearrangements. Although phenotypic variability was observed, we identified a male bias for Childhood Apraxia of Speech associated to 16p11.2 microdeletions. We also reported an elevated frequency of second-site genomic alterations, supporting the model of the second hit to explain the clinical variability associated with CNV syndromes. Our goal was to contribute to the building of a chromosome 16 disease-map based on disease susceptibility regions. The role of the CNVs of chromosome 16 was increasingly made clear in the determination of developmental delay. We also found that in some cases a second-site CNV could explain the phenotypic heterogeneity by a simple additive effect or a pejorative synergistic effect.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 16/genética , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/genética , Anormalidades Múltiplas/classificação , Anormalidades Múltiplas/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas , Deleção Cromossômica , Variações do Número de Cópias de DNA/genética , Deficiências do Desenvolvimento/classificação , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Recombinação Homóloga/genética , Humanos , Lactente , Recém-Nascido , Cariótipo , Masculino , Fenótipo , Duplicações Segmentares Genômicas/genética , Adulto Jovem
9.
Am J Med Genet A ; 170A(5): 1352-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26864752

RESUMO

The 5q14.3 duplication is a rare condition comprising speech and developmental delay, microcephaly, and mild ventriculomegaly. The region 5q14.3 contains several genes but the predominant role for the onset of the neurodevelopmental phenotype has been attributed to MEF2C. We describe the prenatal identification of 5q14.3 duplication, including MEF2C, in a monochorionic twin pregnancy with corpus callosum anomalies, confirmed by autopsy. To the best of our knowledge, this cerebral finding has been observed for the first time in 5q14.3 duplication patients, possibly widening the neurological picture of this scarcely known syndrome. A pathogenetic role of MEF2C overexpression in brain development may be assumed, but further studies are needed.


Assuntos
Encéfalo/fisiopatologia , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Adulto , Autopsia , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Duplicação Cromossômica/genética , Cromossomos Humanos Par 5/genética , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Feto/diagnóstico por imagem , Feto/fisiopatologia , Humanos , Deficiência Intelectual/fisiopatologia , Fatores de Transcrição MEF2/genética , Gravidez , Ultrassonografia Pré-Natal
10.
Diagnostics (Basel) ; 14(16)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39202220

RESUMO

When an increased nuchal translucency (>3.00 mm) is observed during the echographic examination of a foetus in the first trimester of pregnancy, an increased risk of chromosomopathy is considered, and the pregnant woman is offered the possibility of an invasive investigation. Here, we focused our attention on prenatal diagnosis issues in cases of foetuses with cytogenetically balanced reciprocal translocations. We report the finding of a cytogenetically balanced, de facto genomically unbalanced translocation that poses a challenge in a case of prenatal diagnosis, changing the risk of Down syndrome in a Zellweger syndromic spectrum risk (PEX3 deletion). At term, a healthy baby was born. This case teaches that prenatal diagnosis in cases of foetuses at increased risk of chromosomal abnormality imperatively requires molecular investigation in addition to a morphological karyotype.

11.
HGG Adv ; 5(2): 100261, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38160254

RESUMO

The largest multi-gene family in metazoans is the family of olfactory receptor (OR) genes. Human ORs are organized in clusters over most chromosomes and seem to include >0.1% the human genome. Because 369 out of 856 OR genes are mapped on chromosome 11 (HSA11), we sought to determine whether they mediate structural rearrangements involving this chromosome. To this aim, we analyzed 220 specimens collected during diagnostic procedures involving structural rearrangements of chromosome 11. A total of 222 chromosomal abnormalities were included, consisting of inversions, deletions, translocations, duplications, and one insertion, detected by conventional chromosome analysis and/or fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array-CGH). We verified by bioinformatics and statistical approaches the occurrence of breakpoints in cytobands with or without OR genes. We found that OR genes are not involved in chromosome 11 reciprocal translocations, suggesting that different DNA motifs and mechanisms based on homology or non-homology recombination can cause chromosome 11 structural alterations. We also considered the proximity between the chromosomal territories of chromosome 11 and its partner chromosomes involved in the translocations by using the deposited Hi-C data concerning the possible occurrence of chromosome interactions. Interestingly, most of the breakpoints are located in regions highly involved in chromosome interactions. Further studies should be carried out to confirm the potential role of chromosome territories' proximity in promoting genome structural variation, so fundamental in our understanding of the molecular basis of medical genetics and evolutionary genetics.


Assuntos
Cromossomos Humanos Par 11 , Receptores Odorantes , Humanos , Hibridização Genômica Comparativa , Hibridização in Situ Fluorescente , Aberrações Cromossômicas , Translocação Genética/genética , Receptores Odorantes/genética
12.
Genes (Basel) ; 14(9)2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37761840

RESUMO

Complex chromosomal rearrangements are rare events compatible with survival, consisting of an imbalance and/or position effect of one or more genes, that contribute to a range of clinical presentations. The investigation and diagnosis of these cases are often difficult. The interpretation of the pattern of pairing and segregation of these chromosomes during meiosis is important for the assessment of the risk and the type of imbalance in the offspring. Here, we investigated two unrelated pediatric carriers of complex rearrangements of chromosome 7. The first case was a 2-year-old girl with a severe phenotype. Conventional cytogenetics evidenced a duplication of part of the short arm of chromosome 7. By array-CGH analysis, we found a complex rearrangement with three discontinuous trisomy regions (7p22.1p21.3, 7p21.3, and 7p21.3p15.3). The second case was a newborn investigated for hypodevelopment and dimorphisms. The karyotype analysis promptly revealed a structurally altered chromosome 7. The array-CGH analysis identified an even more complex rearrangement consisting of a trisomic region at 7q11.23q22 and a tetrasomic region of 4.5 Mb spanning 7q21.3 to q22.1. The mother's karyotype examination revealed a complex rearrangement of chromosome 7: the 7q11.23q22 region was inserted in the short arm at 7p15.3. Finally, array-CGH analysis showed a trisomic region that corresponds to the tetrasomic region of the son. Our work proved that the integration of several technical solutions is often required to appropriately analyze complex chromosomal rearrangements in order to understand their implications and offer appropriate genetic counseling.

13.
J Biomed Biotechnol ; 2011: 370195, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21318170

RESUMO

The importance of X chromosome in the aetiology of premature ovarian failure (POF) is well-known but in many cases POF still remains idiopathic. Chromosome aneuploidy increase is a physiological phenomenon related to aging, but the role of low-level sex chromosome mosaicism in ovarian function is still undiscovered. Standard cytogenetic analysis was carried out in a total of 269 patients affected by POF: 27 chromosomal abnormalities were identified, including X chromosome and autosomal structural and numerical abnormalities. In 47 patients with 46,XX karyotype we performed interphase FISH using X alpha-satellite probe in order to identify X chromosome mosaicism rate. Aneuploidy rate in the patient group was significantly higher than the general population group. These findings underline the importance of X chromosome in the aetiology of POF and highlight the potential role of low-level sex chromosome mosaicism in ovarian aging that may lead to a premature onset of menopause.


Assuntos
Análise Citogenética/métodos , Insuficiência Ovariana Primária/genética , Adulto , Envelhecimento/genética , Núcleo Celular/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 18/genética , Cromossomos Humanos X/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Interfase , Pessoa de Meia-Idade , Monossomia/genética , Insuficiência Ovariana Primária/patologia
14.
Mol Genet Genomic Med ; 8(1): e1056, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31851782

RESUMO

BACKGROUND: Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array-based detection rate. METHODS: The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. RESULTS: Non-polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non-syndromic neurodevelopmental signs and non-syndromic congenital malformations to a decreased detection rate. CONCLUSIONS: Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes.


Assuntos
Aberrações Cromossômicas , Deficiências do Desenvolvimento/genética , Testes Genéticos/normas , Análise de Sequência com Séries de Oligonucleotídeos/normas , Guias de Prática Clínica como Assunto , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/classificação , Deficiências do Desenvolvimento/diagnóstico , Testes Genéticos/métodos , Genética Médica/organização & administração , Humanos , Itália , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fenótipo , Sensibilidade e Especificidade , Sociedades Médicas/normas
15.
Am J Obstet Gynecol ; 200(6): 636.e1-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19254790

RESUMO

OBJECTIVE: The purpose of this research was to study factors that are involved in centromeric hypomethylation in the pathogenesis of Down syndrome (DS). STUDY DESIGN: This was a case-control study to evaluate the association between methyltetrahydrofolate reductase (MTHFR) C677T and methionine synthetase-reductase (MTRR) A66G polymorphisms and the risk of DS; we compared mothers in Italy who had children with DS and matched control subjects. RESULTS: Seventy-four cases of DS caused by an error in maternal meiosis were compared with 184 matched control subjects. The frequencies of the MTHFR C677T polymorphism were similar between the 2 groups. As regards the MTRR A66G polymorphism, the presence of the mutated G allele either in the heterozygous or homozygous form was significantly more common among mothers of children with DS than among control subjects (odds ratio, 2.21; 95% CI, 1.11-4.40). CONCLUSION: In a population with a high prevalence of the mutated T allele, maternal MTRR A66G, but not MTHFR, polymorphisms are associated with Down syndrome.


Assuntos
Síndrome de Down/genética , Ferredoxina-NADP Redutase/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Mães , Fatores de Risco , Adulto Jovem
16.
Clin Dysmorphol ; 17(1): 35-39, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18049079

RESUMO

Silver-Russell syndrome (SRS) is clinically variable although most cases have several common signs. Different chromosomes and chromosomal regions have been associated with SRS. Maternal uniparental disomy (UPD) of chromosome 7 is responsible for 5-10% of cases, probably because of an imbalance between maternal and paternal imprinted genes and more recently maternal duplication or epimutations in the 11p15 imprinted region have been described. To date, only two patients with maternal UPD7 and a mosaic condition for a supernumerary ring 7 marker have been reported, and we here report a further case. Standard QFQ banding of lymphocytes as well as fluorescence in-situ hybridization analyses were performed to identify and characterize the supernumerary marker. UPD testing was performed on both the patient's and parents' DNA using chromosome 7 microsatellite markers. The patient demonstrated a ring in about 4% of the analysed cells. On the basis of cytogenetic and molecular results, break points were tentatively identified as 7p11.2 and 7q21. Maternal hetero-/iso-UPD and a paternal origin for the supernumerary ring were demonstrated. Clinical data comparison between our patient who has a SRS phenotype and cases with hetero-/iso-UPD7 mat and mosaicism for a paternally derived chromosome 7 ring and previously reported ring 7 cases suggest that the SRS phenotype is probably because of the UPD rather than to the partial trisomy.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 7 , Dissomia Uniparental , Criança , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Síndrome
18.
Ital J Pediatr ; 44(1): 59, 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29801510

RESUMO

BACKGROUND: Currarino syndrome is a rare condition characterized by presacral mass, anorectal malformation and sacral dysgenesis. CASE PRESENTATION: We report the case of a child that presented chronic constipation, encopresis and mycrocephaly. The characteristics were initially compatible with a case of functional constipation and a therapy with polyethylene glycol was prescribed. After a year, because of poor response, a plain abdominal X-ray was performed, detecting sacrum abnormalities. Finally, a CGH-array analysis was performed and a form of Currarino Syndrome caused by a rare 7q36 microdeletion, was diagnosed. CONCLUSION: Occult spinal dysraphism should be suspected in case of poor polyethylene glycol responder constipation, even when evident sacral abnormalities on the physical examination are not detected.


Assuntos
Canal Anal/anormalidades , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Anormalidades do Sistema Digestório/diagnóstico , Anormalidades do Sistema Digestório/genética , Microcefalia/diagnóstico , Microcefalia/genética , Reto/anormalidades , Sacro/anormalidades , Siringomielia/diagnóstico , Siringomielia/genética , Pré-Escolar , Feminino , Proteínas de Homeodomínio/genética , Humanos , Fatores de Transcrição/genética
19.
Mol Cytogenet ; 11: 52, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30202443

RESUMO

BACKGROUND: Copy number variations (CNVs) are largely known today, but their position is rarely established by fluorescence in situ hybridization (FISH) or karyotype analysis. CASE PRESENTATION: We described two families with copy number gain in which FISH analysis with the specific subtelomeric probe of chromosome 4q and 7q evidenced a third signal at band 13p11.2. Genomic study by array comparative genomic hybridization defined the triple dose segment. In the first case, the duplicate tract is free of known genes, in the second one it contained three expressed genes. CONCLUSIONS: The CNV localization on the short arm of an acrocentric chromosome could explain the lack of phenotypic effect, being known the regulatory role of heterochromatin in the position-effect silencing. Furthermore, we would like to underline the importance of using complementary techniques such as FISH and array-CGH to obtain a better definition of genomic rearrangements.

20.
Cancer Genet Cytogenet ; 173(2): 164-9, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17321334

RESUMO

We describe the case of a young woman showing yolk sac tumors (YST) and a Sertoli-Leydig cell tumor (SLCT) in the right ovary, with recurrences in the right adnexum and with hepatic metastasis. To our knowledge, YST and SLCT have never been described as components of the same tumor or reported as associated in the same patient. The patient's karyotype showed the presence of Y chromosome inserted into the 1qh region; the inserted region corresponded to Yq12 heterochromatin. LOH analysis revealed 1p36 paternal allele loss in the proband tumor, thus supporting a germ cell origin for the tumor. The presence of Y heterochromatin in 1qh DNA might induce disturbances in the normal regulation of oncogenes located in 1q.


Assuntos
Cromossomos Humanos Par 1 , Cromossomos Humanos Y , Tumor do Seio Endodérmico/patologia , Neoplasias Ovarianas/patologia , Tumor de Células de Sertoli-Leydig/patologia , Translocação Genética/genética , Carcinoma Endometrioide/patologia , Mapeamento Cromossômico/métodos , Tumor do Seio Endodérmico/genética , Feminino , Heterocromatina/genética , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Perda de Heterozigosidade , Neoplasias Ovarianas/genética , Sitios de Sequências Rotuladas , Tumor de Células de Sertoli-Leydig/genética
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