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In this report, we describe a patient with azoospermia in conjection with de novo ring chromosome 21 and monosomy 21 mosaicism. Inter-phase fluorescence in situ hybridisation ( FISH) studies on uncultured peripheral blood and epithelial cells obtained by buccal smear revealed that 25% of the uncultured blood cells and 11% of the epithelial cells were monosomic for chromosome 21. Y chromosome microdeletion analysis ruled out the presence of any genomic deletions in the azoospermic factor a,b,c regions on the long arm of chromosome Y. Additionally, through subtelomeric FISH analysis, it was found that there was no deletion in the subtelomeric region of ring chromosome 21. Our results indicate that ring chromosome 21 is a rare, but recurrent chromosomal abnormality in male factor infertility. Furthermore, in individuals with ring chromosome 21, defective spermatogenesis is not associated with the deletion of any gene or genes located in the subtelomeric region of chromosome 21. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral dystrophy (FSHD) has a hypomethylation-related epigenetic background and exhibits a different course in male and female patients. The differences between males and females have been linked to the levels of sex hormones. This study is the first to investigate the possible effect of these hormones on methylation status. We hypothesized that the levels of sex-related hormones, estradiol, testosterone, progesterone, and prolactin might be associated with the methylation status of the proximal part of the D4Z4. We also investigated the effect of fT3, folic acid, and vitamin B12 levels. We collected blood from 28 FSHD patients and 28 controls. DNA was extracted from each individual for bisulfite methylation analysis and serum was separated for biochemical analysis of estradiol, testosterone, progesterone, prolactin, fT3, folic acid, and B12 analysis. Methylation analysis was specified to the DR1, 5P regions and the proximal region covering both DR1 and 5P. Methylation levels were compared between FSHD patients and controls. The correlation of methylation levels with estradiol, testosterone, progesterone, prolactin, fT3, folic acid, and B12 was investigated. We found that the 5P region and the proximal region were significantly hypomethylated in FSHD patients compared to the controls, but not the DR1 region. Male patients exhibited a significant reduction in DNA methylation compared to male controls. Older FSHD patients exhibited a notable decrease in fT3 levels and hypomethylation of the 5P region. Analyses of each CpG revealed seven hypomethylated positions that were significantly different from the control group. Two of the positions demonstrated a correlation with progesterone in the control group. With the exception of one position, the methylation levels were inversely correlated with vitamin B12 in FSHD patients. The results of our study indicate that the methylation of the proximal D4Z4 region, particularly at specific positions, may be associated with progesterone. In addition, vitamin B12 may be an indicator of hypomethylation. We suggest that examining position-specific methylations may be a useful approach for the development of epigenetic treatment modalities., (© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

SMA is a neuromuscular disease and occurs primarily through autosomal recessive inheritance. Identification of deletions in the SMN1 gene especially in the exon 7 and exon 8 regions (hot spot), are used in carrier testing. The exact copy numbers of those exons in the SMN1 and SMN2 genes in 113 patients who presented with a pre-diagnosis of SMA were determined using MLPA method. We aimed to reveal both the most common copy number profiles of different SMA types. It was found that the frequency of homozygous deletions in SMN1 was 15.9%, while heterozygous deletions was 16.9%. The most common SMN-MLPA profile was 0-0-3-3. In the cases with homozygous deletion, SMA type III diagnosis was observed most frequently (44%), and the rate of consanguineous marriage was found 33%. Two cases with the same exonic copy number profile but with different clinical subtypes were identified in a family. We also detected distinct exonic deletion and duplication MLPA profiles for the first time. We created "the SMA signature" that can be added to patient reports. Furthermore, our data are important for revealing potential local profiles of SMA and describing the disease in genetic reports in a way that is clear and comprehensive., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Multiple myeloma (MM) is an uncontrolled proliferation of plasma cells and these cells play an important role in the immune system. In this research, we retrospectively analyzed cytogenetic abnormalities in 381 patients with MM. Conventional cytogenetic analysis was successful in 354 patients (92.9%). Chromosomal abnormalities were detected in 31.9% (113/354) and 45.8% (116/253) of patients screened with conventional cytogenetics and FISH, respectively. Of 113 patients with chromosomal abnormalities, 31 patients (27.4%) had hyperdiploid and 26 of 31 patients with hyperdiploidy had both numerical and structural anomalies. On the other hand, non-hyperdiploidy was observed in 62 patients (54.8%). The most common gains of chromosomes were 15, 9, 19 followed by 3, 5, 11, and 21. Whole chromosome losses were also frequent involving Y, 13 and 22 chromosomes. In our patients, 1q gain was determined in a total of 25 patients (22%), including 7 structural abnormalities and 19 unbalanced translocations causing complete or partial duplication of the long arm of chromosome 1. Although the breakpoints were different, t(1;5) balanced translocation and unbalanced translocations of t(1;2), t(1;3), t(1;7), t(1;16) and t(1;19) were observed twice. The most common structural abnormality was the deletion of the short arm of chromosome 13 (13q) or monosomy of chromosome 13 (-13) (24.1%, 61/253) in patients evaluated by FISH. Deletion involving chromosome 17p (del 17p) or monosomy of chromosome 17 (-17) were found in 31 (12.3%) patients. Translocations involving IgH regions were as follows: t(11;14)(q13;q32.33) in 22 (8.7%), t(4;14)(p16.3;q32.33) in 22 (8.7%) and t(14;16)(q32.33;q23.1) in 2 (0.8%) patients. In addition, t(14;17)(q32;q21) translocation was detected in a multiple myeloma patient for the first time in this study. There are a limited number of large study groups including both cytogenetic and FISH findings in MM patients. As the number of these studies increases, it is thought that new cytogenetic data can be guiding especially in clinical risk determination., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Society of Hematology and Blood Transfusion 2019.)

Interstitial deletion of chromosome 11 long arm is a rare event. In most of the interstitial deletions on the long arm of chromosome 11 both the position and the size of these deletions are heterogeneous making a precise karyotype-phenotype correlation. In only a few of the reported cases has the deletion been molecularly characterized. Our patient was a 13-year-old male presented; mental motor retardation, strabismus, myopia, retinopathy, sensorineural hearing loss, a long and triangular face, a broad forehead, hypotelorism, nasal septal deviation, a beaked nose, hypoplastic ala nasie, bilateral low-set ears, a high arched palate, crowded teeth, retrognathia, thin lips, a long neck, and sloping shoulders, hyperactive behavior, pulmonary stenosis and lumbar scoliosis. Conventional cytogenetic analysis revealed 46,XY,del(11)(q14.1-q23.3) karyotype in the patient. Array-CGH analysis of the patient's DNA revealed an interstitial deletion encompassing 33.2 Mb in the 11q14.1-q23.3 genomic region (chr11: 83,161,443-116,401,751 ; Hg19). In this report, we present a patient with an interstitial deletion on the long arm of chromosome 11 that encompassed the 11q14.1-q23.3 region; and, using array-CGH analysis, we molecularly characterized the deleted region.

Purpose: In a chick model of gastroschisis, we aimed to investigate the morphological/cellular, molecular, and ultrastructural changes taking place in gastroschisis-related intestinal damage (GRID)., Methods: 13-Day fertilized eggs were divided into two groups., Control Group: chorio-amnio-allontoic membranes opened and abdominal wall exposed. Gastroschisis group: an anterior abdominal wall defect created after opening membranes. Embryos from both groups were surgically removed on post-fertilization day 19. Intestinal samples were obtained for histopathology, immunohistochemistry, molecular biology, and electron microscopy., Results: The histopathological grade of intestinal damage which primarily involved mucosal structures was significantly higher in the gastroschisis group when compared to the control group (p<0.001). Immunohistochemically, E-cadherin and synaptophysin immunoreactivity in the gastroschisis group was significantly lower than control group (p<0.05 and p<0.01, respectively), whereas there was no significant difference in laminin and type-4 collagen immunoreactivity between the groups (p>0.05). Molecular analyses indicated a significant decrease in NFκB and IκB expression in the gastroschisis group (p<0.05 and p=0.001, respectively). Electron microscopy showed that the gastroschisis group had considerable ultrastructural damage, manifested by apoptosis in all layers., Conclusions: GRID affected all layers but was more prominent in mucosa. The damage may depend on E-cadherin and synaptophysin downregulation. Increased apoptotic activity, associated with decreased NFκB and IκB expression, may be an important component of this multifactorial damaging process., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Chronic myelogenous leukemia (CML) is a clonal hematological disorder, which is characterized by the presence of the classical or variant Philadelphia translocations. During the progression to blastic phase of the disease secondary chromosomal abnormalities may emerge. Such secondary chromosomal abnormalities are nonrandom, the more frequent ones being trisomy 8 and 19, supernumerary i(17q), and extra Philadelphia chromosomes. Furthermore, a minor percentage of the patients may acquire different secondary chromosomal abnormalities including translocations between other chromosomes. We report here a patient with Ph+ CML presenting secondary chromosomal abnormalities including t(4;11)(q21;q23), t(3;3)(q29;q23) and t(11;18)(q10;q10) during the course of CML progression.

We report a patient with a de novo telomeric association between chromosomes 19 and Y in conjunction with mixed gonadal dysgenesis. The patient was first admitted to the clinic because of abnormal external genitalia. Laparoscopic evaluation revealed (1) a rudimentary uterus, one fallopian tube, and a small gonad resembling an ovary on the right side, and (2) an immature fallopian tube, a vas deferens, and a gonad resembling a testis on the left side. Conventional cytogenetic analysis performed on cultivated peripheral blood cells, and tissue obtained from the phallus and a gonadal structure which resembled a testis revealed two different cell lines with the 46,X,tas (Y;19)(p11.3;q13.4) and 45,X karyotype. Y chromosome microdeletion analysis showed that the patient did not have any genomic deletions in the AZFa, b, c, or SRY regions on the long arm of the Y chromosome. This is the first report of a patient with mixed gonadal dysgenesis that is accompanied by a telomeric association between chromosomes 19 and Y with 45,X mosaicism.

We report here a prenatal case with de novo supernumerary marker chromosome originating from chromosome 17 in non-mosaic form resulting in normal pregnancy outcome. In this case, a 26-year-old pregnant woman was referred for amniocenthesis and microdeletion Fluorescence In Situ Hybridization (FISH) testing at 18 weeks of gestation due to history of a previous child with Angelman Syndrome. PWS/AS region deletion was excluded by FISH. A de novo supernumerary, non-satellited, monocentric marker chromosome was detected during conventional cytogenetic analysis. With the use of FISH testing, it was found that the marker chromosome originated from chromosome 17. Additionally, the marker chromosome was found not to contain the Smith-Magenis and Miller Dieker syndrome regions. After detailed review of the literature, genetic counseling was given to the family, and the family decided to continue the pregnancy to term. A female child was born at term without any phenotypical abnormalities and clinical complications. Follow-up at 15 months-of-age revealed no developmental abnormalities. To our knowledge, our patient is the first reported prenatal case with a de novo monocentric, supernumerary marker chromosome derived from chromosome 17 in a non-mosaic form that resulting in normal pregnancy outcome.

We have performed a retrospective array-based comparative hybridization (array-CGH) study on 41 acute leukemia samples [n=17 acute lymphoblastic leukemia (ALL) patients only at diagnosis, n=3 ALL patients both at diagnosis and relapse; n=20 acute myeloid leukemia (AML) patients only at diagnosis and n=1 AML patient both at diagnosis and relapse] using an Agilent 44K array. In addition to previously detected cytogenetic aberrations, we observed cryptic aberrations in 95% of ALL and 90.5% of AML cases. ALL-specific recurrent abnormalities were RB1 (n=3), PAX5 (n=4), and CDKN2B (n=3) deletions; AML-specific recurrent abnormalities were HOXA9 and HOXA10 (n=2) deletions and NOTCH1 duplication (n=2). Recurrent duplication of the ELK1 oncogene was observed in both ALL (n=2) and AML (n=3) cases. Our results demonstrate that oligo-array CGH (oaCGH) is an effective method for defining copy number alterations and identification of novel recurring unbalanced abnormalities. At least for now, however, the use of oaCGH for routine diagnosis still has some restrictions.

Infantile spasms (IS) is the most severe and common form of epilepsy occurring in the first year of life. At least half of IS cases are idiopathic in origin, with others presumed to arise because of brain insult or malformation. Here, we identify a locus for IS by high-resolution mapping of 7q11.23-q21.1 interstitial deletions in patients. The breakpoints delineate a 500 kb interval within the MAGI2 gene (1.4 Mb in size) that is hemizygously disrupted in 15 of 16 participants with IS or childhood epilepsy, but remains intact in 11 of 12 participants with no seizure history. MAGI2 encodes the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 that interacts with Stargazin, a protein also associated with epilepsy in the stargazer mouse.

Bardet-Biedl syndrome (BBS) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. Patients with BBS are also at increased risk for diabetes mellitus, hypertension, and congenital heart disease. BBS is known to map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although these loci were all mapped on the basis of an autosomal recessive mode of inheritance, it has recently been suggested-on the basis of mutation analysis of the identified BBS2, BBS4, and BBS6 genes-that BBS displays a complex mode of inheritance in which, in some families, three mutations at two loci are necessary to manifest the disease phenotype. We recently identified BBS1, the gene most commonly involved in Bardet-Biedl syndrome. The identification of this gene allows for further evaluation of complex inheritance. In the present study we evaluate the involvement of the BBS1 gene in a cohort of 129 probands with BBS and report 10 novel BBS1 mutations. We demonstrate that a common BBS1 missense mutation accounts for approximately 80% of all BBS1 mutations and is found on a similar genetic background across populations. We show that the BBS1 gene is highly conserved between mice and humans. Finally, we demonstrate that BBS1 is inherited in an autosomal recessive manner and is rarely, if ever, involved in complex inheritance.