Genetic analysis of a Chinese pedigree with 18q21.2-q22.3 duplication and deletion in two offspring respectively resulting from a maternal intrachromosomal insertion / 中华医学遗传学杂志

OBJECTIVE@#To provide prenatal diagnosis, pedigree analysis and genetic counseling for a pregnant woman who had given birth to a child featuring global developmental delay.@*METHODS@#A pregnant woman who underwent prenatal diagnosis at the Affiliated Hospital of Southwest Medical University in August 2021 was selected as the study subject. Peripheral blood samples were collected from the woman, her husband and child, in addition with amniotic fluid sample during mid-pregnancy. Genetic variants were detected by G-banded karyotyping analysis and copy number variation sequencing (CNV-seq). Pathogenicity of the variant was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was traced in the pedigree to assess the recurrence risk.@*RESULTS@#The karyotypes of the pregnant woman, her fetus, and affected child were 46,XX,ins(18)(p11.2q21q22), 46,X?,rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat and 46,XY,rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat, respectively. Her husband was found to have a normal karyotype. CNV-seq has revealed a 19.73 Mb duplication at 18q21.2-q22.3 in the fetus and a 19.77 Mb deletion at 18q21.2-q22.3 in her child. The duplication and deletion fragments were identical to the insertional fragment in the pregnant woman. Based on the ACMG guidelines, the duplication and deletion fragments were both predicted to be pathogenic.@*CONCLUSION@#The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree.

Clinicopathologic Study of Chromosomal Aberrations in Ocular Adnexal Lymphomas of Korean Patients

PURPOSE: The incidence and clinical correlation of MALT1 translocation and chromosomal numerical aberrations in Korean patients with ocular adnexal mucosa associated lymphoid tissue (MALT) lymphoma have not yet been reported. We investigated the incidence and clinicopathologic relationship of these chromosomal aberrations in ocular adnexal MALT lymphomas in a Korean population. METHODS: Thirty ocular adnexal MALT lymphomas were investigated for the t(11;18) API2-MALT1, t(14;18) IgH-MALT1 translocations and chromosomes 3 and 18 aneuploidies using fluorescence in situ hybridization. Patient medical records were reviewed retrospectively for information on demographics and clinical characteristics, including treatment response. RESULTS: The MALT1 gene rearrangement was found in one out of 30 cases. The t(14;18) IgH-MALT1 translocation was demonstrated in only one case (3.3%), and the t(11;18) API2-MALT1 translocation was not found in any of the cases. Trisomy 3 was observed in three ocular adnexal MALT lymphomas (10.0%), and five cases showed trisomy 18 (16.7%). Translocation positive cases also showed trisomy 18. One case of tumor relapse showed trisomy 18 only in the recurrent biopsies. There were no statistically significant correlations between chromosomal aberrations and clinical characteristics and treatment responses. CONCLUSIONS: Translocations involving the MALT1 gene are not common in Korean ocular adnexal MALT lymphomas. The t(14;18) translocation was detected in only one out of 30 cases, and the t(11;18) translocation was not found at all. Furthermore, the chromosomal aberrations found in this study had no prognostic implications.

Rapid detection of chromosome X, Y, 13, 18, and 21 aneuploidies by primed in situ labeling/synthesis technique.

AIMS AND OBJECTIVE: Primed in situ labeling/synthesis (PRINS) technique is an alternative to fluorescent in situ hybridization for chromosome analysis. This study was designed to evaluate the application of PRINS for rapid diagnosis of common chromosomal aneuploidy. MATERIALS AND METHODS: We have carried out PRINS using centromere specific oligonucleotide primers for chromosome X, Y, 13, 18 and 21 on lymphocyte metaphase and interphase cells spread. Specific primer was annealed in situ, followed by elongation of primer by Taq DNA polymerase in presence of labeled nucleotides. Finally, reaction was stopped and visualized directly under fluorescent microscope. RESULTS: Discrete centromere specific signals were observed with each primer. CONCLUSION: PRINS seems to be a rapid and reliable method to detect common chromosome aneuploidy in peripheral blood lymphocyte metaphase and interphase cells.

Preimplantation genetic screening (PGS) in infertile female age > or = 35 years by fluorescence in situ hybridization of chromosome 13, 18, 21, X and Y.

INTRODUCTION: It is common in infertile couples that the female partner age > or = 35 years, that some of them require assisted reproductive technology (ART) for their treatment, it is also well known that in this female age group increases the chance of chromosome aneuploidy in offsprings. It is known that the antenatal diagnosis may have the ethical dilemma and psychological impact. Therefore, the preimplantation genetic screening (PGS) may have a role in this ART group. OBJECTIVE: The present study had the objective to compare the incidence of normal, abnormal embryos and also aneuploidy of each chromosome, i.e. 13, 18, 21, X and Y between 2 subgroups of age i.e. the age 35-39 years and 32-39 years vs. the age > or = 40 years in both female and male partners respectively. MATERIALS AND METHOD: This prospective study was performed in 20 infertile couples attending the Fertility Clinic at Thammasat University Hospital during the years 2006-2007 of which the female partner aged > or = 35 years had to use the ART. The PGS was performed by FISH technique with 5 probes to detect the 13, 18, 21, X and Y chromosomes. The comparative analysis was made between 2 subgroups of both female and male partner aged, as mentioned above in the incidence of normal, abnormal embryos and aneuploidy of each chromosome by Chi-square test and Fisher's exact test with statistical significance if p < 0.05. RESULTS: The abnormal embryos in the female partner age > or = 40 years were higher than those of the age 35-39 years (72.4% vs. 52.5%, p = 0.07) but with no statistical significance. No different results were obtained in the comparable male partner age groups (56.8% vs. 61.4%, p = 0.66). The normal female and male embryos in the female partner age 40 years were lower than those of the age 35-39 years (10.4% vs. 25.4%, p = 0.08 and 17.2% vs. 22.1%, p = 0.60 respectively) but with no statistical significance. The normal female and male embryos in the male partner age > or = 40 years and the age 32-39 years were also compared with no significant differences (20.5% vs. 20.5%, p = 1.00 and 22.7% vs. 18.2%, p = 0.60, respectively). The percentage of embryos with aneuploidy of chromosome 18 in the female partner age > or = 40 years was significantly higher than that of the age 35-39 years (72.0% vs. 45.0%, p = 0.003). The pregnancy rate in the presented PGS study was 12.5% but unfortunately was associated with a high abortion rate of 100%. CONCLUSION: It was found in the present study that the incidence of abnormal embryos trend to increase in the female partner aged > or = 40 years compared to the aged 35-39 years although with no statistical significance. However, the incidence of embryos with aneuploidy of chromosome 18 was higher in females aged > or = 40 years with statistical significance, whereas the male partner age had no impact on the abnormality or normality of the embryo. The abortion rate was very high (100%) probably may be due to inadequate choice of probes, inappropriate fixation technology and small sample size. However, the results obtained in this study indicate that the PGS should be considerably performed with strong indication only.

Patent Ductus Arteriosus and Pulmonary Valve Stenosis in A Patient with 18p Deletion Syndrome

We report on a patient with a partial deletion on the short arm of chromosome 18 (del 18p), who presented with dysmorphic features and delayed developmental milestones as well as with a patent ductus arteriosus (PDA) and pulmonary valve stenosis (PS). Several forms of congenital heart disease (CHD) are found in about 10% of patients with del (18p), but coexisting PDA and PS have not been reported. Del (18p) must be considered in patients with characteristic phenotypic abnormalities and congenital heart disease, including a combination of PDA and PS.

Thai girl with ring chromosome 18 (46XX, r18).

Chromosomal anomalies occur in 0.4% of live births. Ring chromosomes have been found for all human chromosomes and when it is replacing a normal chromosome, it results as a partial monosomy. The phenotype often overlaps that seen in comparable deletion syndromes of the same chromosomes. In the present report the authors describe the clinical manifestations of a girl with ring chromosome 18 (46XX,r18) including dysmorphic features, failure to thrive, global delay of development, hypothyroidism, atopic dermatitis, bilateral chronic otitis media, aortic regurgitation with patent foramen ovale and immunoglobulin A deficiency.

Constitutional tetrasomy 18p.

We present here the first case of constitutional tetrasomy 18p from India. A 3 year old female with developmental delay and dysmorphic features revealed 47,XX,+mar karyotype. The small meta-centric marker chromosome was identified as i(18p) with m-FISH followed by m-BAND. Parents and a normal sibling of the proband revealed normal karyotype. There was history of mental retardation and dysmorphic features in four cases on paternal side; however, their karyotype was also normal.

Diagnóstico y manejo perinatal de trisomia 18 / Diagnosis and perinatal management of trisomy 18

El síndrome de Edwards es un cuadro de baja frecuencia y muy mal pronóstico, por lo cual el diagnóstico prenatal es indispensable para tomar una conducta adecuada. Presentamos 9 casos en los cuales se sospechó este diagnóstico por ultrasonido con confirmación pre o postnatal. Destacan por su frecuencia la presencia de retardo de crecimiento intrauterino, polihidramnios y el signo de mano traslapada. La trisomía 18 tiene una mortalidad perinatal de 89 por ciento con un 78 por ciento de partos vaginales

Anillo del cromosoma 18 en un lactante con cariotipo 46, XY/46, XY, r(18), hijo de madre con mosaicismo para el anillo cromosómico / An [46,XY/46 XY,r(18)] infant born from a mother with r(18) mosaicism

Introducción. La alteración autosómica por una formación en anillo del cromosoma 18 es una aberración poco frecuente que se encuentra en relación con malformaciones fenotípicas, aunadas a problemas neurológicos, anormalidades óseas en extremidades y deficiencia de hormona de crecimiento. Caso clínico. Se presenta un paciente masculino de 3 meses de edad con dismorfias craneofaciales treboliformes con suturas cerradas, frente amplia ovoide, comisuras palpebrales pequeñas y ambigüedad de genitales, extremidades con manos pequeñas, dedos sobrepuestos, pies pequeños, ortejos con sindactilia bilateral. El paciente presentó 2 líneas celulares, con una fórmula cromosómica en mosaico 46,XY/46,XY, r(18). La madre del paciente tiene también mosaico para el cromosoma en anillo. Conclusión. Dentro de las alteraciones cromosómicas, el anillo del cromosoma autosómico número 18 es rara, las principales alteraciones fenotípicas en este estudio estuvieron relacionadas con el desarrollo neurológico, genital y de las extremidades