Prenatal genetic diagnosis of a case with ring chromosome 13 / 中华医学遗传学杂志

OBJECTIVE@#To carry out cyto- and molecular genetic analysis for a fetus with a ring chromosome identified through non-invasive prenatal testing (NIPT).@*METHODS@#A pregnant woman presented at the Shengjing Hospital Affiliated to China Medical University on May 11, 2021 was selected as the study subject. Maternal peripheral blood sample was screened by NIPT, and G-banded chromosomal karyotyping was carried out on amniotic fluid and peripheral blood samples from the couple. The fetus and the pregnant woman were also subjected to genomic copy number variation sequencing (CNV-seq), chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) assay.@*RESULTS@#NIPT result suggested that the fetus had monomeric mosaicism or fragment deletion on chromosome 13. G banded chromosomal analysis showed that both the fetus and its mother had a karyotype of 47,XX,der(13)(pter→p11::q22→q10),+r(13)(::p10::q22→qter::), whilst her husband had a normal karyotype. FISH has verified the above results. No abnormality was detected with CNV-seq and CMA in both the fetus and the pregnant woman.@*CONCLUSION@#The ring chromosome 13 in the fetus has derived from its mother without any deletion, duplication and mosaicism. Both the fetus and the pregnant woman were phenotypically normal.

Phenotypical characterization of 13q deletion syndrome: Report of two cases.

Patients with 13q deletion syndrome are characterized with different phenotypical features depending on the size and location of the deleted region on chromosome 13. These patients fall into three groups: In Group 1, deleted region is in the proximal and does not extend into q32; in Group 2, deleted region involves proximal to the q32 and in Group 3 q33‑q34 is deleted. We present two cases with 13q syndrome with two different deleted region and different severity on clinical features: One case with interstitial deletion belongs to the Group 1 with mild mental retardation and minor malformations and the other case with terminal deletion belongs to Group 3 with moderate to severe mental retardation and major malformations.

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.

A new recurring chromosome 13 abnormality in two older patients with de novo acute myeloid leukemia: An Indian experience.

We report here two cases of trisomy 13 in acute myeloid leukemia M1 subtype. short-term unstimulated bone marrow and peripheral blood lymphocyte culture showed 47, XY, +13 in all metaphase plates and trisomy 13 was confirmed with whole chromosome paint probes. Trisomy 13 in AML-M1 is a rare numerical abnormality. This is the first Indian report of sole trisomy 13 in AML-M1. Here, we present two cases of elder male patients, which may constitute a distinct subtype.

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.

Prenatal ultrasonographic findings in "trisomy 13".

OBJECTIVE: To evaluate the accuracy of prenatal ultrasonographic diagnosis in fetuses with trisomy 13. MATERIAL METHOD: The present study consisted of all fetuses diagnosed of trisomy 13 and delivered at Ramathibodi Hospital between 1997 and 2006. RESULTS: There were 15 cases of trisomy 13. Twelve cases (80.0%) were detected by prenatal ultrasonographic examination, and 3 cases (20.0%) were missed. Mean maternal age was 31.4 years old. Sixty-six percent were diagnosed in 2" trimester (mean 19.4 weeks). The earliest gestational age for detection was 12 weeks 6 days. The most common abnormal ultrasonographic findings were holoprosencephaly (46.7%), and facial defects (40.0%). CONCLUSION: The accuracy of prenatal sonographic diagnosis in trisomy 13 fetuses was 80%. The most sensitive prenatal ultrasonographic findings in trisomy 13 were holoprosencephaly and facial defects.

Comparative genomic hybridization (CGH) analysis of chromosomal aberrations in Iranian patients with invasive ductal carcinoma breast cancer.

INTRODUCTION: Breast cancer is one of the most common cancers in women; however, due to the complexity of chromosomal changes, limited data are available regarding chromosomal constitution. MATERIALS AND METHODS: In this study, Comparative Genomic Hybridization (CGH) was used on 16 Iranian patients diagnosed with invasive ductal breast carcinomas. RESULTS: 12 samples had abnormal CGH results (75%), including 21 types of chromosomal imbalance. The most prevalent were chromosomal gain of +1q, +17q, +8q and chromosomal loss of -13q. All three cases with DNA loss at chromosome 13q (-13q) had lymph node metastasis. CONCLUSIONS: CGH is able to detect chromosomal abnormalities which are difficult to identify by conventional cytogenetic techniques. More studies on a larger sample size may help to confirm or rule out any possible correlation between 13q monosomy and lymph node metastasis, which could result in establishing new strategies for prevention and early detection of invasive breast tumors.

Karyotyping in retinoblastoma--a statistical approach.

PURPOSE: Karyotype analysis in hereditary retinoblastoma is considered to be of marginal value in risk prediction due to uncertainties in the assessment of 13q14 deletions. However, it is a low cost genetic test for retinoblastoma in developing countries. In the present study, the results of karyotype analysis were refined by a statistical method to overcome limitations. METHODS: Karyotype analysis was performed by trypsin-Giemsa banding and naked eye karyotyping for 33 bilateral, 25 unilateral and one regressed retinoblastoma patients. The percentage of metaphases with 13q14 deletions in each case was plotted on a scatter diagram. Normalization of the data was achieved by log transformation and the results were statistically analyzed by one-sample 't' test using SPSS version 9.0. RESULTS: Seven samples had 13q14 deletion percentages above the cutoff value. One-sample 't' test showed significance (p< 0.001). By this method, two unilateral and five bilateral patients had 13q14 deletions, constituting 11.8 % of cases. CONCLUSION: For accuracy, statistical analysis should be considered as an adjunct in karyotyping.

Partial trisomy 13 with features similar to C syndrome.

We report a case of partial trisomy 13 with trigonocephaly, upslant eyes, long smooth philtrum, polydactyly, agenesis of right kidney and mild developmental delay. In this family phenotypically normal mother had pericentric inversion of chromosome 13 and the child (proband) received recombinant 13 from the mother. Genetic counselling of the family for reproductive risks and testing siblings of the mother for detection of balanced carriers is essential.

Molecular-genetic analysis of two cases with retinoblastoma: benefits for disease management.

Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of the world. We studied histopathological, chromosomal and molecular-genetic data of two retinoblastoma patients from India. The two patients, one with bilateral and the other with unilateral retinoblastoma, underwent complete ophthalmic examination, cytogenetic study, retinoblastoma gene (RB1) mutational analysis and RB1 promoter region methylation screening. In the bilateral retinoblastoma patient deletion of chromosome region 13q14 in peripheral blood lymphocytes and a hemizygous novel 8-bp deletion in exon 4 of RB1 in tumour sample were observed. In the unilaterally affected patient CGA to TGA transition protein truncation mutations were observed in exons 8 and 14 of RB1.

Genetic profile of 81 retinoblastoma patients from a referral hospital in southern India.

PURPOSE: To determine chromosomal abnormalities and inheritance pattern in patients with retinoblastoma from a referral hospital in southern India. MATERIALS AND METHODS: Eighty-one retinoblastoma patients from 78 families were included in this study. Peripheral venous blood was taken for chromosomal analysis and pedigree was ascertained for segregation analysis. RESULTS: Male to female ratio was 1.7:1, 55.56% were bilateral retinoblastoma, the mean age of onset was 12.37 months in bilateral and 33.07 months in unilateral cases (p=0.048). Majority (90.12%) had sporadic inheritance and 6.17% had autosomal dominant inheritance. In chromosomal abnormalities, 8.33% had 13q14 deletion, three cases had de novo balanced translocations. CONCLUSION: The age of onset of the disease was much earlier in the bilateral cases compared to unilateral cases. Sporadic inheritance was predominant while only a small percentage of patients had autosomal dominant inheritance. The percentage of patients with 13q14 deletion was higher than reported in the literature and three novel chromosomal translocations were observed. This is one of the largest series of cases reported from India.

A Case of del(13)(q22) with Multiple Major Congenital Anomalies, Imperforate Anus and Penoscrotal Transposition

"13q-"syndrome is known to have widely variable manifestations, including retinoblastoma, mental and growth retardation, malformation of brain and heart, anal atresia, and anomalies of the face and limbs. Here we report a case of del(13)(q22) with multiple major congenital anomalies for the first time in Korea. The patient was born at 36+4 weeks of pregnancy by caesarian section. Birth weight was 1490g. On examination the following features were noted: - imperforate anus, ambiguous genitalia (bifid scrotum, penoscrotal transposition, hypospadia), syndactyly of toes, absence of thumbs, abnormal facies (dolichocephaly, telecanthus, large low set ears, saddle nose, high arched palate, micrognathia). Neurocranial ultrasonography showed atrophy of the corpus callosum and multiple calcifications. He died at 14 days. Post-mortem autopsy findings showed cholestasis and fatty metamorphosis of liver, abnormal lobulation (Rt:2, Lt:1) and lymphangiectasis of the lung, VSD, ASD, PDA of heart, and acute tubular necrosis of kidney. Cytogenetic studies was confirmed to 46,XY,del(13) (q22) by Giemsa banded chromosomes from peripheral blood lymphocytes.

Autism and mental retardation: the genetic relationship and contribution

Autism, a neurodevelopmental disorder first described in 1943, is reviewed. The signs and symptoms of the disorder are described together with the etiological factors. The evidence for a genetic etiology of autism and its association with other genetic disorders are discussed. Possible candidate genes for autism are described

Assignments of the tyrosinase related protein-1 and -2 genes to human chromosome bands 9p23 and 13q32.1 by in situ hybridization

To determine the precise chromosomal localization of tyrosine related protein-1 and -2 (TRP-1 and TRP-2) genes by fluorescence in situ hybridization, we used DNAs isolated from human bacterial artificial chromosome clones. They contain genomic sequences with approximately 120 kb inserts for TRP-1 and TRP-2. The TRP-1 and TRP-2 genes were assigned to human chromosome bands 9p23 and 13q32.1, respectively. These results confirmed the previously mapped location for the TRP-1 gene and more precisely located the TRP-2 gene, which had previously been mapped to chromosome 13q31-q32.