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BACKGROUND: Maturity-onset diabetes of the young comprises a large group of autosomal inherited gene mutations. Maturity-onset diabetes of the young subtype 5 is caused by mutations in the HNF1B gene. This gene is expressed in the early phase of embryonic development in the pancreas, kidneys, liver, and genital tract; therefore, kidney or urinary tract malformations are associated with diabetes mellitus. The 17q12 deletion syndrome is a cause of maturity-onset diabetes of the young subtype 5 that should be considered. CASE PRESENTATION: We present the case of a 35-year-old Hispanic female patient with a history of bicornuate uterus and polycystic renal disease that required kidney transplant. She had insulin-dependent diabetes, with her mother, maternal grandmother, and great-grandmother showing a similar clinical manifestation. Molecular analysis showed a deletion in chromosome 17q12 involving 15 genes, including HNF1B. Therefore, a diagnosis of deletion syndrome was made. CONCLUSIONS: The 17q12 deletion syndrome represents a rare genetic syndrome that involves different genes, including HNF1B. Principally, it is characterized by the combination of genitourinary tract malformations and diabetes mellitus, similar to our patient.
Assuntos
Transtornos Cromossômicos , Diabetes Mellitus Tipo 2 , Gravidez , Humanos , Feminino , Adulto , Deleção Cromossômica , América Latina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/diagnóstico , Transtornos Cromossômicos/genética , SíndromeRESUMO
BACKGROUND: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. METHODS: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. RESULTS: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/µL vs 16.1µL in the non-thymus group (p=0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. CONCLUSION: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure.
Assuntos
Subpopulações de Linfócitos T/fisiologia , Linfócitos T/fisiologia , Timectomia , Timo/cirurgia , Adolescente , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 22/imunologia , Feminino , Citometria de Fluxo , Humanos , Lactente , Contagem de Linfócitos , Masculino , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
BACKGROUND: Array-based comparative genome hybridization (array CGH) is a first-line test used in the genetic evaluation of individuals with multiple anomalies, developmental delays, and cognitive deficits. In this study, we analyzed clinical indications and findings of array CGH tests of Colombian individuals forwarded to a reference laboratory over a period of seven years in order to evaluate the diagnostic performance of the test in our population. RESULTS: The results of 1374 array CGH analyses of Colombian individuals were referred to the Andean Reference Institute in Colombia (Instituto de Referencia Andino) during a 7-year period (2009-2015). Chromosomal imbalances were detected in 488 cases (35%), whereas 121 cases were classified as nonpathogenic variants, 65 cases (4.7%) were classified as variants of uncertain significance, and 302 cases (22%) were classified as abnormal or pathogenic. The most common findings in the abnormal and/or pathogenic set were deletions, followed by duplications and complex rearrangements. Variants in the carrier status of autosomal recessive diseases were identified as incidental findings in 29 subjects (2%). CONCLUSIONS: Clinical indications preceding the referral of aCGH in Colombian patients are not standardized and result in unexpected pathogenic variants as well as secondary findings that need careful interpretation. Development of local infrastructure will probably improve the communication between all stakeholders, to ensure accurate clinical diagnoses.
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Submicroscopic deletions in chromosome 19 have been rarely reported. We reported a male patient presenting with neurodevelopmental delay and facial dysmorphisms with a de novo 19p13.11p13.12 deletion of approximately 1.4 Mb. To date, there are seven cases with deletions overlapping the 19p13.11-p13.12 region described in the literature. A region of 800 kb for branchial arch defects in the proximal region of 19p13.12, and another minimal critical region of 305 kb for hypertrichosis, synophrys, and protruding front teeth have been proposed previously. We suggest that the shortest region of overlap could be refined to an approximately 53 kb region shared within all patients, encompassing part of BRD4 and AKAP8L genes and the AKAP8 gene. Based on the genotype-phenotype correlation of the present case and cases with overlapping deletions described in the literature, it was possible to recognize a consistent phenotype characterized by microcephaly, ear abnormalities, rounded face, synophrys, arched or upwardly angulated eyebrows, short nose, anteverted nares, prominent cheeks, teeth abnormalities, and developmental delay.
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Cromossomos Humanos Par 19/genética , Deficiências do Desenvolvimento/fisiopatologia , Hipertricose/genética , Deficiência Intelectual/fisiopatologia , Proteínas de Ancoragem à Quinase A/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/fisiopatologia , Proteínas de Ciclo Celular , Criança , Deleção Cromossômica , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Humanos , Hipertricose/diagnóstico , Hipertricose/fisiopatologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Microcefalia/diagnóstico , Microcefalia/genética , Microcefalia/fisiopatologia , Proteínas Nucleares/genética , Fatores de Transcrição/genéticaRESUMO
Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation.
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Cognição/fisiologia , Síndrome de DiGeorge/diagnóstico , Deficiência Intelectual/etiologia , Tetralogia de Fallot/etiologia , Adolescente , Idade de Início , Síndrome de DiGeorge/fisiopatologia , Humanos , MasculinoRESUMO
Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation.
El síndrome del cromosoma 22q11.2, también conocido como supresión o síndrome de DiGeorge o síndrome velocardiofacial, es uno de los síndromes más comunes de anomalías múltiples en los seres humanos. Este síndrome es comúnmente causado por una microdeleción del cromosoma 22 en q11.2 banda. Aunque este trastorno genético muestra varias anomalías clínicas y diferentes grados de compromiso orgánico, las características clínicas que han atraído la mayor atención son el comportamiento y el desarrollo, porque las personas con síndrome de deleción 22q11.2 tienen un riesgo 30 veces mayor de desarrollar esquizofrenia. Hay diferentes opiniones sobre el desarrollo cognitivo, y comúnmente se se ha observado un deterioro cognitivo en lugar de un inicio temprano de discapacidad intelectual. Presentamos un caso de síndrome de deleción 22q11.2 tanto con la evaluación temprana de discapacidades intelectuales leves como con la tetralogía de Fallot como única manifestación física.
Assuntos
Fibrinogênio/química , Nanoestruturas/química , Cristalização/métodos , Liofilização/métodos , Umidade , Conformação Proteica , Espalhamento a Baixo Ângulo , Solubilidade , Termodinâmica , Água/química , Difração de Raios X/métodos , Raios XRESUMO
Introduction: During the past few decades, the number of diseases identified to be caused by chromosomal microdeletions has increased quickly, bringing a new and crucial role for cytogenetics on the diagnosis of these conditions. The purpose of this study was to identify and characterize chromosomal microdeletions associated with malformation syndromes and intellectual disability. Methods: We retrospectively evaluated a consecutive series of samples from a cohort of 598 subjects with clinical symptoms of a microdeletion syndrome, including the deletion of chromosomes 4p16.3, 5p15.2, 5q35, 7q11.23, 8q24.12, 15q11.2, 16p13.3, 17p13.3, 17p11.2,2, and 22q11.2, as investigated by fluorescence in situ hybridization (FISH). Array-based comparative genomic hybridization (array-CGH) was performed on 25 samples with microdeletions. Results: A total of 598 samples were evaluated from patients whose clinical phenotypes were most indicative of 22q11.2 deletion syndrome (29.10%), Prader-Willi syndrome (23.41%), Angelman syndrome (16.89%), and Williams-Beuren syndrome (14.72%). In 142 of the samples (23.75%), a chromosomal imbalance associated with phenotypic abnormalities was found. The deletion of 7q11.23 was the most frequent (8.03%), followed by del22q11.2 (5.68%) and del15q11.2 (5%). Conclusion: Our study reinforces the idea that the effort to improve the capacity to perform molecular cytogenetic investigations associated with a qualified clinical evaluation is crucial for the detection and precise characterization of submicroscopic chromosome deletions, bringing benefits to patients, relatives, and genetic counselors. It also contributes to the continuing education of cytogeneticists and to the knowledge of chromosomal rearrangements associated with genomic disorders.
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Humanos , Aberrações Cromossômicas , Deleção Cromossômica , Anormalidades Congênitas , Análise Citogenética , Deficiência Intelectual/genética , Predisposição Genética para Doença , Transtornos Cromossômicos/diagnóstico , Citogenética/educação , Síndrome de Angelman/genética , Síndrome de Prader-Willi/genética , Síndrome de Williams/genéticaRESUMO
We report on a patient carrying a 17q21.31 microdeletion and exhibiting many common syndrome features, together with other clinical signs which have rarely or never been described to date. The detected 695-kb 17q21.31 deletion is larger than in most previously reported cases but is still probably the result of recombination between flanking low-copy repeats. Due to the complexity of the patient's clinical condition, together with the presence of 3 previously unreported symptoms, namely chronic anemia, cervical vertebrae arthrosis and vertebrae fusion, this case is an important addition to the existing knowledge about the 17q21.31 microdeletion syndrome.
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Introduction: Neurofibromatosis-Noonan syndrome is a clinical entity considered an extended Neurofibromatosis phenotype generally caused by different types of intragenic mutations at the NF1 gene. About 5%-10% of patients with neurofibromatosis diagnosis carry chromosomal microdeletions involving NF1, often presenting with a more severe phenotype than that observedin the patients carrying intragenic mutations; however, anticipating the presence of a deletion based only in the phenotype is not straightforward. Patient and Methods: Here we investigated by oligoarray-CGH (aCGH) the presence of a submicroscopic genomic rearrangement in a patientwith a clinical picture of Neurofibromatosis, and other characteristics compatible with Noonansyndrome. Results: The aCGH analysis revealed a germline de novo ~1.3 Mb microdeletion at 17q11.2 encompassing other coding genes besides the NF1 gene. Discussion: Up to now, thenumber of reported patients with Neurofibromatosis-Noonan syndrome carrying NF1 microdeletions is quite small. The continuous identification of patients carrying 17q11.2 deletions canhelp to establish a reliable genotype-phenotype relationship in this syndrome
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Humanos , Neurofibromatoses , Síndrome de NoonanRESUMO
Monosomy 1p36 is the most common subtelomeric microdeletion syndrome with an incidence rate estimated to be 1 in 5000 births. A hypothesis of a similarity between patients with 1p36 deletion and those with Prader-Willi syndrome and the existence of two different phenotypes for 1p36 microdeletion has been suggested. The main objective of the present study was to determine the existence of 1p36 microdeletion in a sample of patients with mental retardation, obesity and hyperphagia who tested negative by the methylation test for Prader-Willi syndrome. Sixteen patients (7 females, 9 males), 16-26 years old, were evaluated with high-resolution cytogenetic analysis at 550-850 band levels and with 11 polymorphic microsatellite markers located in the 1p36 region. All patients had normal cytogenetic and molecular results. The results obtained by high-resolution cytogenetic methodology were confirmed by the molecular analyses. We did not detect a 1p36 microdeletion in 16 subjects with the Prader-Willi-like phenotype, which reinforces that no correlation seems to exist between Prader-Willi-like phenotype and the 1p36 microdeletion syndrome.