Un caso de deleción parcial 1p36. 1 y trisomía parcial 6p diagnosticadas por cariotipo / A case of partial 1p36. 1 deletion and partial trisomy 6p diagnosed by karyotype

La deleción de la región cromosómica 1p36 es una de las anomalías subteloméricas más frecuentes y causa rasgos dismórficos distintivos. Por otro lado, la trisomía distal del brazo corto del cromosoma 6 es una anormalidad cromosómica poco frecuente de fenotipo variable. Objetivo: Presentar el caso de un paciente con ambas alteraciones cromosómicas, y resaltar la vigencia e importancia del cariotipo como herramienta diagnóstica en dismorfología. Caso clínico: Lactante de 2 meses de edad con múltiples anomalías craneofaciales, hemangioma en la nuca, fosita sacra, acortamiento rizomélico, pies y manos pequeños, criptorquidia unilateral izquierda e hipotonía. Además, antecedente de restricción del crecimiento intrauterino. Producto del octavo embarazo de una mujer G8A7C1 de 28 años. Con estos hallazgos inespecíficos en el fenotipo se solicitó cariotipo que mostró una deleción parcial de 1p36.1 y una trisomía parcial de cromosoma 6p. Conclusión: El cariotipo convencional sigue siendo una herramienta importante para el etiológico en pacientes con anomalías congénitas (múltiples), mostrando en este caso una deleción parcial de 1p36.1 y una trisomía parcial de cromosoma 6p, alteraciones cromosómicas estructurales.

The deletion of chromosomal region 1p36 is one of the most common sub-telomeric microdeletion syndromes and has distinctive dysmorphic features. On the other hand, partial trisomy of the short arm of chromosome 6 is a rare chromosomal abnormality with a variable phenotype. Objective: To report a case with both chromosome abnormalities, and to highlight the importance of the karyotype as a diagnostic tool in dysmorphology. Clinical case: The case of is presented of a two month-old infant with several craniofacial anomalies, neck haemangioma, sacral pit, rhizomelic shortening, small hands and feet, left unilateral cryptorchidism, and hypotonia. The infant also suffered intrauterine growth restriction and is the product of the eighth pregnancy of a 28 years old woman. Due to the unspecific findings in phenotype, a karyotype was requested, which showed a partial deletion of 1p36.1 and a partial trisomy of chromosome 6. Conclusion: The development of new techniques in molecular biology has improved diagnostic possibilities in medical genetics. However, the traditional karyotype remains as an important diagnostic tool in patients with multiple congenital anomalies.

Una revisión actualizada del síndrome de deleción (monosomía) 1p36 / An updated review of 1p36 deletion (monosomy) syndrome

El síndrome de monosomía 1p36 forma parte del grupo de enfermedades conocidas como «enfermedades de baja prevalencia¼ o «enfermedades raras¼. El objetivo del presente trabajo es revisar los hallazgos de los principales estudios realizados en niños diagnosticados con el síndrome de monosomía 1p36. El fenotipo del síndrome de deleción (monosomía) 1p36 delineado desde 1997 incluye rasgos craneofaciales dismórficos: fontanela anterior grande, cejas rectas, ojos hundidos, epicanto, raíz/puente nasal anchos, hipoplasia del tercio medio facial, orejas implantadas anormalmente, filtrum largo y barbilla puntiaguda; alteraciones neurológicas: convulsiones e hidrocefalia (en casos aislados); malformaciones cerebrales observadas en imágenes por resonancia magnética (IRM): ensanchamiento ventricular, ensanchamiento de espacios subaracnoideos, alteraciones morfológicas del cuerpo calloso, entre otras. La IRM evidencia en algunos pacientes atrofia cortical, retraso en la mielinización, áreas multifocales hiperintensas, leucomalacia periventricular y heterotopia periventricular. Estos pacientes cursan con discapacidad intelectual, retrasos en el desarrollo motor, de la comunicación, del lenguaje, en el área personal-social y en la conducta adaptativa. También se observan alteraciones en el sistema auditivo, visual, cardiaco, endocrino, genitourinario, dermatológico y esquelético. Conclusiones: Existen datos de aproximadamente 100 casos en el mundo desde 1981. Esta enfermedad rara es el síndrome más común de microdeleción subtelomérica. La técnica de hibridación in situ con fluorescencia y la técnica de hibridación genómica comparativa (array-CGH) son las que mejor permiten su diagnóstico. Por el momento no existe ningún tratamiento médico efectivo para esta enfermedad.

The Monosomy 1p36 deletion syndrome is part of the group of diseases known as Rare Diseases. The objective of the present work is to review the characteristics of Monosomy 1p36 deletion syndrome. The monosomy 1p36 deletion syndrome phenotype includes: dysmorphic craniofacial features; large anterior fontanelle, unibrow, deep-set eyes, epicanthus, wide nasal root/bridge, mandible hypoplasia, abnormal location of the pinna, philtrum and pointed chin; neurological alterations: seizures and hydrocephalus (in some cases). Cerebral malformations: ventricular hypertrophy, increased subarachnoid space, morphological alterations of corpus callosum, cortical atrophy, delays in myelinisation, periventricular leukomalacia and periventricular heterotopia. These alterations produce intellectual disability and delays in motor growth, communication skills, language, social and adaptive behaviour. It is Hearing and vision impairments are also observed in subjects with this syndrome, as well as alterations of cardiac, endocrine and urinary systems and alterations at skin and skeletal level. Conclusions: Approximately 100 cases have been documented since 1981. This rare disease is the most common sub-telomeric-micro-deletion syndrome. In situ hybridization with fluorescence (FISH) and array-comparative genomic hybridization (CGH-array) are at present the two best diagnostic techniques. There is currently no effective medical treatment for this disease.

1p36 deletion syndrome confirmed by fluorescence in situ hybridization and array-comparative genomic hybridization analysis / 소아과

Pediatric epilepsy can be caused by various conditions, including specific syndromes. 1p36 deletion syndrome is reported in 1 in 5,000–10,000 newborns, and its characteristic clinical features include developmental delay, mental retardation, hypotonia, congenital heart defects, seizure, and facial dysmorphism. However, detection of the terminal deletion in chromosome 1p by conventional G-banded karyotyping is difficult. Here we present a case of epilepsy with profound developmental delay and characteristic phenotypes. A 7-year- and 6-month-old boy experienced afebrile generalized seizure at the age of 5 years and 3 months. He had recurrent febrile seizures since 12 months of age and showed severe global developmental delay, remarkable hypotonia, short stature, and dysmorphic features such as microcephaly; small, low-set ears; dark, straight eyebrows; deep-set eyes; flat nasal bridge; midface hypoplasia; and a small, pointed chin. Previous diagnostic work-up, including conventional chromosomal analysis, revealed no definite causes. However, array-comparative genomic hybridization analysis revealed 1p36 deletion syndrome with a 9.15-Mb copy loss of the 1p36.33-1p36.22 region, and fluorescence in situ hybridization analysis (FISH) confirmed this diagnosis. This case highlights the need to consider detailed chromosomal study for patients with delayed development and epilepsy. Furthermore, 1p36 deletion syndrome should be considered for patients presenting seizure and moderate-to-severe developmental delay, particularly if the patient exhibits dysmorphic features, short stature, and hypotonia.

Primary Spinal Cord Oligodendroglioma with Postoperative Adjuvant Radiotherapy: A Case Report

Primary spinal cord oligodendrogliomas are rare tumors comprising two percent of all spinal cord tumors. Although a treatment guideline has yet to be established, maximal surgical resection is primary in the treatment of spinal cord oligodendrogliomas. Adjuvant radiotherapy has remained controversial, and it is unclear whether chemotherapy adds any benefit. In this case report, the authors present a 24-year-old male who had a seven-year history of left leg weakness and a radiating pain in both legs. Magnetic resonance image (MRI) showed an intramedullary mass at the T4-T8 level. He underwent subtotal removal of the tumor and pathologic diagnosis revealed a WHO grade II oligodendroglioma. The patient was treated with radiotherapy postoperatively and followed up with MRI annually. Clinical and radiological status of the patient had been stationary for four years after the surgery. The five-year follow-up MRI showed an increase in the size and extent of the residual tumor. Despite radiological progression, considering that symptoms and the performance status of the patient had remained unchanged, further treatment has not been performed. Given the clinical outcome of this patient, close observation after subtotal removal with adjuvant radiotherapy is one of the acceptable treatment options for WHO grade II spinal cord oligodendrogliomas.

Detection of growth phenotype and blood biochemical parameters of wild type-derived chromosome 1 substitution mouse strain / 中国实验动物学报

Objective To analyze the growth phenotype and blood biochemical parameters of chromosome 1 substi-tution mouse strain(CSS1), and investigate their potential of QTL mapping .Methods Body weight, body length, tail length, organ weight of the CCS1 mice were measured at different days to create a growth curve while blood biochemical in -dexes were measured at about the 80th day.Results The CCS1 mice were different from C57BL/6 mice in several inde-xes.Compared with the C57BL/6 mice during different developmental stages , six strains including B6-Chr1KM mice were significantly different in body weight .There were five strains including B6-Chr1CM mice significantly different with C57BL/6 mice in body length, and all of the CSS1 mice were significantly different from C57BL/6 mice in tail length.Part of CCS1 mice were significantly different from C57BL/6 mice in the weight of liver, spleen, kidney and brain.The ALT of female B6-Chr1CM mice was significantly higher than that in the C 57BL/6 mice.The ALP of female B6-Chr1HZ mice was signifi-cantly higher than that in the male C57BL/6 and B6-Chr1KM mice, and was significantly lower than that in the C57BL/6 mice.The TB of male B6-Chr1CM, B6-Chr1SMX and B6-Chr1HZ mice was significantly higher than that of the C 57BL/6 mice.The TG of male B6-Chr1SMX mice and male B6-Chr1TW mice was significantly higher than that in the C 57BL/6 mice. Conclusions The phenotype of Chr1 CSS mice is quite different from commonly used inbred strain C 57BL/6 mice.CCS1 mice show great potential in QTL mapping for their characteristic growth phenotype and blood biochemical indexes .

A Case of Chromosome 1q44 Deletion with Microcephaly and Multiple Congenital Anomalies / 대한주산의학회잡지

The 1q terminal deletion syndrome is a rare chromosomal disorder which was first reported by Mankinen et al. in 1976. This disorder has shown to have broad and diverse clinical phenotypes. Specific phenotypes of 1q terminal deletion syndrome include microcephaly, seizures, psychomotor retardation, growth retardation, abnormalities of extremities, corpus callosum, heart and genitalia. Although this disorder has diverse clinical manifestations, almost all cases of 1q44 deletion syndrome have growth, psychomotor, and mental retardation and progressive microcephaly. The first diagnosis of 1q44 deletion syndrome in Korea was made by fluorescent in situ hybridization analysis in a 4-month-old girl with craniofacial anomalies, multiple congenital anomalies, and growth and psychomotor retardation. We report the second domestic case of 1q44 deletion syndrome with cleft palate, facial dysmorphism, single umbilical artery, foot abnormality, progressive microcephaly, growth and psychomotor retardation which was confirmed by microarray for comparative genomic hybridization. We also compare this case with previously reported cases of 1q44 deletion syndrome.

A chromosome 1q44 deletion in a 4-month-old girl; The first report in Korea / 소아과

The deletion of the distal long arm of chromosome 1 is associated with a characteristic facial appearance and a pattern of associated malformations. Characteristic manifestations include a round face with prominent 'cupid's bow' and downturned corners of the mouth, thin vermilion borders of lips, a long upper lip with a smooth philtrum, a short and broad nose, epicanthal folds, apparently low-set ears, micrognathia, microcephaly, abnormal hands and feet, variable cardiac or genital anomalies, moderate to severe mental retardation, and growth retardation. Using fluorescent in situ hybridization (FISH) analysis to map precisely the deletion, we present a case of chromosome 1q44 deletion with craniofacial characteristics, multiple congenital anomalies, and growth and psychomotor retardation. In comparison with other reported cases of 1q43-44 deletion, the subject does not show hydrocephalus, seizure, syn- or polydactyly of hands, and a urogenital anomaly. However, an arachnoid cyst, pinpoint dimple on the midline of the forehead, a right-sided supernumerary nipple and auricular pit, polydactyly of the right foot, adducted thumb, and flexion restriction of the proximal interphalangeal joint with a simian line in both hands were observed additionally.

Application of molecular biomarkers in differential diagnosis of benign and malignant follicular thyroid tumors / 中华内分泌代谢杂志

Twenty-nine thyroid tissue samples were collected from patients with thyroid nodules.The total RNA were extracted,the gene expressions of TFF3,HMGA2,C1orf24,and DDIT3 were detected by RT-PCR.In comparison with normal thyroid tissues,the expression of C1orf24 mRNA was decreased in the follicular thyroid adenoma (FTA) group,but increased in the follicular thyroid carcinomas (FTC) group.The expressions of DDIT3 and HMGA2 mRNA were increased in both FTA and FTC groups,and were even higher in the latter.The expressions of TFF3 mRNA level were decreased in FTA and FTC.The data suggested that molecular markers C1ort24,DDIT3,HMGA2,and TFF3 in thyroid tissue seem to be helpful in the differential diagnosis between follicular adenomas and carcinomas.

Genesis and clinic significance of chromosome 1 abnormality in hematologic malignancies / 白血病·淋巴瘤

[Objective] To analyze the frequency,type of chromosome 1 clonal abnormalities in hematologic malignancies,and to understand the clinical and biological significance of its occurrence.[Methods] Retrospectively analyzed of 256 cases of patients with hematologic malignancies cytogenetic R banding karyotype analysis [Results].Summarized the abnormal chromosomel karyotype and clinical data summary and combined with literature review.Results There were 25 samples with clonal disorder of chromosome 1 in 256 cases of patients with malignant hematologic disease,accounting for 9.8 percent of the total samples,including ALL-L2,ANLL-M2,MDS,MM,lymphoma with bone marrow involvement,CML with accelerated phase and blast crisis,plasma cell leukemia and chronic myelogenous monocytic leukemia.The types of the clonal disorder included chromosome 1 translocation with other chromosomes[including 3cases with t(1;19),and 2 cases with t(1;4)],there were 7 cases with chromosome 1 the increase or missing partly, and 7cases with increasing a full or partial deletion of chromosome 1,and also 3 cases with isochromosome of 1q.t(1 ; 19) can be found in B lymphocyte proliferative diseases,while t(1;14) was found in T-ALL.The clinical efficacy and short survival were found in 20 patients with chromosome 1 clonal abnormalities. [Conclusion] Chromosome I clonal abnormalities in hematologic malignancies is common in acute leukemia,MDS,MM,and atypical abnormality is more than typical abnormality.It is common in chromosome 1 translocation with other chromosomes,lq-trisomy.The recurrent chromosome abnormalities is t (1;19) and t (1;14),which is related with the leukemia immune phenotype.lq-trisoiny and amplification of 1q21 is effective in the therapy and guide the prognosis of MDS and MM.

The Expression of Folate Sensitive Fragile Sites in Patients with Bipolar Disorder

PURPOSE: Genetic factors are known to be important in the etiology of bipolar disorder (BD). The fragile sites (FSs) are a very interesting subject for the study of clinical disorders. The aim of this study was to evaluate fragile sites seen in patients with bipolar disorder and find a correlation between some fragile sites and bipolar disorder. PATIENTS AND METHODS: The frequencies of folate sensitive FSs were compared in short-term whole blood cultures from bipolar patients and from normal individuals. RESULTS: The rate of FS expression in the patients was considerably higher than in the controls (p < 0.001). Several chromosome regions including 1p36, 1q21, 1q32, 3p25, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22 and Xq26 were represented considerably more often in the patients than in the controls (p value between 0.001 to 0.036). Among these FSs, the sites 1p36, 1q21, 3p25, 7q22, 7q32, and 14q24 were not observed in other studies. CONCLUSION: These regions can be the most active of hot spots in the genomes of bipolar patients, and may harbor important genes associated with BD.

Characterization of microsatellite markers covering chromosome 1 in the Korean and Japanese populations / 대한치과교정학회지

Microsatellite markers are considered to be very promising genetic markers for genetic linkage analysis. The majority of the markers are as informative as in Caucasians but there are significant ethnic differences in the genetic variations. In order to investigate the genetic variations in the Korean and Japanese populations and their ethnic differences, 51 microsatellite marker loci spanning the whole human chromosome 1 were arranged from a commercially available set (ABI PRISM Linkage Mapping Set-HD5, Applied Biosystems, Foster City, CA, USA), and then determined the allelic frequencies and heterozygosities for these marker loci in the 96 unrelated Korean subjects and 96 unrelated Japanese subjects. Of all 51 markers tested, significant differences were observed when microsatellite allele frequency pattern of Korean was compared with those of Caucasian, while this pattern was highly similar between Korean and Japanese populations. Our data indicate that an extensive verification of public microsatellite markers in a particular population study should be undertaken prior to their linkage studies. Moreover, this information should facilitate genetic linkage studies of various hereditary diseases, especially in the Koreans and Japanese.

Chromosomal Alterations in Hepatocellular Carcinoma Cell Lines Detected by Comparative Genomic Hybridization / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: There have only been a few cytogenetic studies of hepatocellular carcinoma (HCC), and so far, no consistent specific chromosomal abnormalities have been described. Here, we have used comparative genomic hybridization (CGH), a powerful molecular cytogenetic technique for detecting changes of the copy number throughout the genome, to screen for genetic alterations in HCC cell lines. The CGH results were compared with those derived from G-banding and chromosome painting. MATERIALS AND METGODS: Conventional cytogenetic analyses were performed on five HCC cell lines, SNU-354, SNU-368, SNU-387, SNU-449 and SNU-475, using a G- banding staining technique. In CGH, equal amounts of differently labeled DNA from the cell lines, and normal reference DNA, were hybridized simultaneously to normal metaphase chromosomes. They were visualized by different fluorochromes, and the signal intensities quantified separately as gray levels along the single chromosomes. The over- and under-represented DNA segments were determined by computation of ratio images and average ratio profiles. To confirm the CGH results, florescence in situ hybridization (FISH), with chromosome specific painting, was performed using indirectly labeled chromosome specific paints. RESULTS: Complex unbalanced chromosomal aberrations, which could not be identified reliably by conventional cytogenetics in HCC cell lines, were successfully resolved by CGH analysis. CGH results were validated using FISH with chromosome specific probes. In HCC cell lines, gains in DNA copy number were more common than losses. The most prominent changes were gains of 1q12- qter (80% of cases), 1q41-qter (100%), 7 (80%), 8q12-qter (60%), 8q23-qter (80%) and 20q12-qter (60%). Recurrent losses were mapped on 4q13-qter (60%), 16q12-qter (60%), 16q21-qter (80%), 13q12-q14.2 (60%) and Yq11.2 (100%). All four male HCC cell lines showed loss or rearrangement of the Y chromosome. CONCLUSION: Conventional cytogenetics, CGH and FISH using painting probes, represent complementary approaches that, when employed in combination, could greatly facilitate the comprehensive analysis of chromosomal imbalances in HCC cell lines. Our results suggest the existence of an oncogene, or protooncogenes, on chromosome 1q41-qter, and the tumor suppressor genes on Yq11.2, that play a role in the development and/or progression of hepatocellular carcinogenesis.

Analysis of Chromosome-specific Aneusomy in Breast Tumor by Using Fluorescence in Situ Hybridization

PURPOSE: Several studies have used FISH (fluorescence in situ hybridization) to analyze aneuploids in various solid tumors. FISH, using chromosome-specific, alpha-stellite DNA probes, can be used to detect aneusomy in interphase and/or metaphase cells. The aims of this study were to compare the FISH cen tromere signals from benign breast tumors and to those from breast cancers and to evaluate the clinico pathologic parameters and the aneusomic patterns involving chromosomes 1, 11, and 17 in breast cancers. METHODS: FISH was performed on touch preparations from 15 benign breast-tumor and 29 breast-cancer specimens. The frequency of aneusomy, measured by nondisomy, was determined for chromosomes 1, 11, and 17 through the use of chromosome-specific alpha-stellite DNA probes. The frequency of chromosome- specific aneusomy was then correlated with clinicopathologic parameters, including tumor size, lymph- node involvement, estrogen receptor, and nuclear grade. RESULTS: Only one of the 15 benign breast tumors was shown to be aneusomic for chromosome 1. The other 14 cases of the benign breast tumors showed no evidence of aneusomy for any of the 3 chromosomes. In breast cancers, however, 26 of the 29 cases (90%) were exhibited aneusomy of at least 1 of the 3 chromosomes evaluated and chromosome 1 was most frequently aneusomic (26 of 29 cases (90%)). The present study also suggested a possible correlation between the numeric abnormality of chromosome 1 and estrogen receptor levels. No significant correlations with tumor size, regional lymph-node metastasis, and nuclear grade were observed. CONCLUSION: These findings suggest that chromosome-specific aneusomy is more frequently observed in breast cancers than in benign breast tumors and that aneusomy of chromosome 1 correlates with estrogen receptor levels.