A diagnostic clinical genetic study of craniofacial dysmorphism

A diagnostic evaluation of craniofacial anomalies, either isolated or as part of a genetic syndrome was conducted on 25 patients [8 females, 17 males], age range 2 months to 47 years. Complete genetic examination, pedigree analysis, anthropometric measurements and radiological studies were carried out. Cytogenetic studies included fluorescence in situ hybridization [FISH]when indicated. In all, 15 patients had chromosomal abnormalities. Five patients had unbalanced chromosome rearrangements and six had chromosome markers. Three patients were FISH-positive for William syndrome and one was positive for Prader-Willi syndrome. Ten patients had monogenic disorders. Five were diagnosed as craniosynostosis syndromes. We conclude that minor features are useful for making a diagnosis of congenital anomalies

Download Full-text

Genetic and Dental Study of Patients with Celiac Disease

Journal of Clinical Pediatric Dentistry ◽

10.17796/jcpd.35.2.8613257m26g47713 ◽

2010 ◽

Vol 35 (2) ◽

pp. 217-223 ◽

Cited By ~ 3

Author(s):

Soliman Ouda ◽

Omar Saadah ◽

Omar El Meligy ◽

Sumer Alaki

Keyword(s):

Celiac Disease ◽

Autosomal Recessive ◽

Pedigree Analysis ◽

Clinical Findings ◽

Autosomal Recessive Mode ◽

Enamel Hypoplasia ◽

Clinical Genetic ◽

Genetic Examination ◽

Mode Of Inheritance ◽

Saudi Patients

Objectives: The aim of this work was to study the pattern of inheritance of celiac disease in a group of Saudi patients and to compare oral mucosal and dental clinical findings in these patients to those of healthy controls.Study design: Fifty patients suffering from celiac disease were screened for dental evaluation. They were subjected to clinical genetic examination, pedigree construction, oral mucosal and dental clinical evaluation. Results: An autosomal recessive mode of inheritance was evident in some of the studied cases,while others showed sporadic occurrence. Oral mucosal and dental clinical examinations revealed recurrent oral ulcerations, enamel hypoplasia in most of the celiac disease patients. Conclusions: Pedigree analysis of families is important to identify the mode of inheritance. Oral mucosal and dental clinical examinations are important in diagnosing and monitoring cases of celiac disease.

Download Full-text

A case report of concomitant myopathy, adrenal insufficiency, and mental retardation linked with deletion of Xp21

Problems of Endocrinology ◽

10.14341/probl2017635329-333 ◽

2017 ◽

Vol 63 (5) ◽

pp. 329-333

Author(s):

Elizaveta M. Orlova ◽

Marina V. Kurkina ◽

Leila S. Sozaeva ◽

Maria A. Kareva ◽

Ilya V. Kanivets ◽

...

Keyword(s):

Mental Retardation ◽

Muscular Dystrophy ◽

Adrenal Insufficiency ◽

Chromosomal Abnormalities ◽

Gene Dosage ◽

Chromosome Region ◽

Glycerol Kinase ◽

Genetic Syndrome ◽

Monogenic Disorders ◽

Congenital Adrenal Hypoplasia

Contiguous gene syndromes (CGS) are the disorders caused by chromosomal abnormalities: deletions, duplications, or other complex rearrangements that alter gene dosage. Initially, before their chromosomal nature is elucidated, they may be misdiagnosed as monogenic disorders depending on the leading clinical symptom cluster. The altered chromosomal region in individuals with this condition is typically less than 5 Mb in size and sometimes cannot be identified by conventional karyotyping. Patients present with signs of the diseases associated with each individual monogenic disorder. The Xp21-linked genetic syndrome, or glycerol kinase deficiency (GKD) (MIM 300474), is an example of this syndrome [1–3]. The genes coding for glycerol kinase (GK), congenital adrenal hypoplasia (NR0B1), and dystrophin (DMD) follow each other in the Xp21.2—p21.3 region. Deletions of an X-chromosome region may cause several monogenic disorders in one patient, including primary adrenal insufficiency and hypogonadotropic hypogonadism as a result of deletion in the NR0B1 gene, Duchenne muscular dystrophy (or a milder form, Becker muscular dystrophy) resulting from deletion in the dystrophin gene, and mental retardation as a result of deletion in the glycerol kinase gene. We report a case of concomitant myopathy, adrenal insufficiency, and mental retardation linked with deletion of Xp21.

Download Full-text

Simultaneous genotypic and immunophenotypic analysis of interphase cells using dual-color fluorescence: a demonstration of lineage involvement in polycythemia vera

Blood ◽

10.1182/blood.v80.4.1033.1033 ◽

1992 ◽

Vol 80 (4) ◽

pp. 1033-1038 ◽

Cited By ~ 53

Author(s):

CM Price ◽

EJ Kanfer ◽

SM Colman ◽

N Westwood ◽

AJ Barrett ◽

...

Keyword(s):

Polycythemia Vera ◽

Fluorescent In Situ Hybridization ◽

Chromosomal Abnormalities ◽

Myeloproliferative Disorders ◽

Chromosome 8 ◽

Dual Fluorescence ◽

Interphase Cell ◽

Molecular Alterations ◽

Interphase Cells

Abstract Fluorescent in situ hybridization has become a useful technique by which chromosomal abnormalities may be shown in interphase cells. We present a dual-fluorescence method whereby a chromosomal and immunophenotypic marker can be visualized simultaneously in the same interphase cell. Two patients with the myeloproliferative disorder polycythemia vera and trisomy for chromosome 8 have been studied using this technique and selective involvement of the myeloid and erythrocyte lineages has been shown by the detection of the trisomy in immunophenotyped cells. Simultaneous analysis of genotype and immunophenotype in individual cells from patients with myeloproliferative disorders or leukemia may help identify the developmental and lineage status of cells in which molecular alterations have resulted in clonal advantage.

Download Full-text

Application of the FISH Technique to Visualize Sex Chromosomes in Domestic Cat Spermatozoa

Animals ◽

10.3390/ani11072106 ◽

2021 ◽

Vol 11 (7) ◽

pp. 2106

Author(s):

Barbara Kij-Mitka ◽

Halina Cernohorska ◽

Svatava Kubickova ◽

Sylwia Prochowska ◽

Wojciech Niżański ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Sex Chromosomes ◽

Chromosomal Abnormalities ◽

Molecular Cytogenetics ◽

Molecular Probes ◽

Domestic Cat ◽

Fish Technique ◽

Y Chromosomes

Fluorescence in situ hybridization is a molecular cytogenetics technique that enables the visualization of chromosomes in cells via fluorescently labeled molecular probes specific to selected chromosomes. Despite difficulties in carrying out the FISH technique on sperm, related to the need for proper nuclear chromatin decondensation, this technique has already been used to visualize chromosomes in human, mouse, cattle, swine, horse, and dog spermatozoa. Until now, FISH has not been performed on domestic cat sperm; therefore, the aim of this study was to visualize sex chromosomes in domestic cat sperm. The results showed the presence of X and Y chromosomes in feline spermatozoa. The procedure used for sperm decondensation and fluorescence in situ hybridization was adequate to visualize chromosomes in domestic cat spermatozoa and, in the future, it may be used to determine the degree of chromosomal abnormalities in these gametes.

Download Full-text

De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-020-02587-3 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Ismael F. Alarbeed ◽

Abdulsamad Wafa ◽

Faten Moassass ◽

Bassel Al-Halabi ◽

Walid Al-Achkar ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Chromosomal Abnormalities ◽

Molecular Genetic ◽

Type A ◽

Chemotherapeutic Treatment ◽

Acute Myeloid ◽

New Mutations

Abstract Background Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. Case presentation Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. Conclusions To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.

Download Full-text

Sample preparations are important for fluorescence in situ hybridization of cells biopsied from preimplantation embryos

Zygote ◽

10.1017/s0967199412000639 ◽

2013 ◽

Vol 22 (3) ◽

pp. 300-304

Author(s):

Lifei Li ◽

Xuehong Zhang ◽

Weihua Wang

Keyword(s):

Sample Preparation ◽

Chromosomal Abnormalities ◽

Genetic Diagnosis ◽

Preimplantation Embryos ◽

Human Embryos ◽

Fixation Time ◽

Preparation Technique ◽

Hypotonic Solution ◽

Modified Method

SummaryFluorescence in situ hybridization (FISH) is a cytogenetic technology used to detect chromosomal abnormalities in preimplantation human embryos. However, its efficiency is not stable due to improper sample preparation. The present study was designed to modify the current sample preparation technique and then to evaluate its efficiency in human preimplantation genetic diagnosis (PGD). Day 3 cleavage embryos as well as day 5 and 6 blastocysts were biopsied by mechanical aspiration method. In the present study, two methods were used for sample preparation of the biopsied cells. Method I was the traditional method, in which each blastomere was placed in a hypotonic solution for 5 min and then fixed on glass slides. The slides were kept at room temperature before the FISH procedures. Method II was a modified method, in which all blastomeres were placed individually in hypotonic solution drops covered by oil for at least 5 min and then fixed on slides with 0.1% Tween/HCl. After fixation, the slides were kept at –20°C for at least 30 min before the FISH procedures. The two methods were compared in terms of time consumption and proportions of blastomeres with FISH signals. In total, 329 blastomeres from day 3 embryos were fixed by Method I with an average fixation time of 8–10 min for each blastomere. By contrast, with Method II, 362 blastomeres were fixed and the average time was 3–4 min for each blastomere. After FISH, more nuclei had signals with Method II (97.2%) than with Method I (86.9%). All cells that were biopsied from blastocysts and prepared with Method II had FISH signals. However, Method I was not suitable for the fixation of multiple cells biopsied from blastocysts as cells were not traceable during the fixation. The present study indicates that proper sample preparation is critical for obtaining FISH signals in cells biopsied from preimplantation human embryos; hence these modifications can increase the efficiency of human PGD.

Download Full-text

A rare case of discrete aortic coarctation in Williams-Beuren syndrome. Diagnostic and therapeutic considerations

La Pediatria Medica e Chirurgica ◽

10.4081/pmc.2015.120 ◽

2015 ◽

Vol 37 (2) ◽

Cited By ~ 1

Author(s):

Savina Mannarino ◽

Eitan Keizman ◽

Michele Pasotti ◽

Alessia Claudia Codazzi ◽

Elisabetta De Sando ◽

...

Keyword(s):

Aortic Coarctation ◽

Genetic Disorder ◽

Pulmonary Stenosis ◽

Rare Event ◽

Facial Dysmorphism ◽

Gene Deletions ◽

Genetic Syndrome ◽

Surgical Interventions ◽

Elastin Gene

Williams-Beuren syndrome (WBS) is a genetic disorder caused by elastin gene deletions, and is characterized by cardiovascular malformations, primarily including supravalvular aortic stenosis and peripheral pulmonary stenosis. We report a case of a neonate who developed severe discrete aortic coarctation, underwent multiple surgical interventions, and was subsequently diagnosed with WBS. Severe discrete aortic coarctation is a rare event in WBS newborns. An abnormally thick aortic wall is present in these patients and is the basis of the failure of the classical approach towards coarctation repair, which consists of end-to-end anastomosis as first surgical choice. Our case, and a very few similar previously documented cases, have all demonstrated recoarctation, which only aortic patch implantation was able to successfully repair. In light of this, we would also like to underline the importance of early WBS diagnosis. Therefore, even in mild syndromic phenotype such as low birth weight or facial dysmorphism that raise the suspicion of a genetic syndrome, it is advisable to perform fluorescent <em>in situ</em> hybridization analysis rather than merely karyotypic one.

Download Full-text

ANALYSIS OF COMPLEX CHROMOSOMAL ABNORMALITIES IN A CASE OF MULTIPLE MYELOMA USING SPECTRAL KARYOTYPING

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i9.27133 ◽

2018 ◽

Vol 11 (9) ◽

pp. 9

Author(s):

Perumal Govindasamy ◽

Pooja S Kulshreshtha ◽

Prabu Pandurangan ◽

Anil Tarigopula ◽

Jayarama S Kadandale ◽

...

Keyword(s):

Multiple Myeloma ◽

Chromosomal Abnormalities ◽

Bone Marrow Cells ◽

Spectral Karyotyping ◽

Multicolor Fish ◽

Genetic Abnormalities ◽

Prognostic Outcome ◽

Conventional Cytogenetics ◽

Marrow Cells

Objective: It was proposed to determine the chromosomal abnormalities in a 49-year-old male patient with multiple myeloma (MM) employing both conventional and advanced molecular cytogenetic techniques.Methods: GTG-banding and spectral karyotyping (SKY) on fixed metaphases obtained from LPS-stimulated bone marrow cells and interphase fluorescence in situ hybridization (iFISH) on unsorted marrow cells were carried out to identify genetic markers of prognostic significance.Results: The abnormal chromosomes observed through conventional cytogenetics could be resolved with SKY technique. The translocation t(4;14) (p16;q32) indicating FGFR3/IGH fusion and deletion of 13q14.3 was noticed using iFISH. The genetic abnormalities confirmed a poor prognostic outcome in the patient who died within 6 months of diagnosis.Conclusion: This report emphasizes the need for multicolor FISH techniques besides iFISH to resolve complex abnormalities and to identify cryptic aberrations of importance in risk stratification of MM patients.

Download Full-text

1q44 microdeletion syndrome: A new case with potential additional features

Romanian Journal of Medical Practice ◽

10.37897/rjmp.2021.1.16 ◽

2021 ◽

Vol 16 (1) ◽

pp. 92-96

Author(s):

Elena-Silvia SHELBY ◽

◽

Tanser HUSEYINOGLU ◽

Georgeta CARDOS ◽

Liliana PADURE ◽

...

Keyword(s):

Developmental Delay ◽

Grey Matter ◽

Chromosome 1 ◽

Global Developmental Delay ◽

Microdeletion Syndrome ◽

Genetic Syndrome ◽

Skeletal Involvement ◽

Craniofacial Dysmorphism ◽

Prenatal Hydronephrosis ◽

One Year

1q44 microdeletion syndrome (1q44 monosomy) is a newly described genetic syndrome characterized by the haploinsufficiency of a 6 Mb locus on the long arm of chromosome 1. The main features are global developmental delay, seizures, hypotonia and craniofacial dysmorphism. With a prevalence below one in a million cases, this syndrome is very rare and, hence, often passes undiagnosed. We present the case of a one year old girl admitted to our hospital with global developmental delay and several congenital abnormalities suggesting a plurimalformative syndrome. Microarray analysis detected a 967 kb deletion in the 1q44 region as well as a a 530 kb microduplication in the 14q31.1q31.2 region, the latter having unknown clinical significance as it contains no currently known OMIM genes. The patient’s phenotype was in accordance to 1q44 microdeletion syndrome. Furthermore, after studying the 1q44 microdeletion syndrome cases reported so far in the literature, we have noticed that our patient presented previously undescribed features of this syndrome, namely prenatal hydronephrosis, bifid hallux and grey matter heterotopy. Based on the cerebral, renal and skeletal involvement in 1q44 microdeletion syndrome, we suspect these might be additional, previously unreported features of 1q44 microdeletion syndrome.

Download Full-text