scholarly journals Ring Chromosome 4 in a Child with Multiple Congenital Abnormalities: A Case Report and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
C. S. Paththinige ◽  
N. D. Sirisena ◽  
U. G. I. U. Kariyawasam ◽  
L. P. C. Saman Kumara ◽  
V. H. W. Dissanayake
Keyword(s):  
Clinical Features ◽  
Congenital Abnormalities ◽  
De Novo ◽  
Ductus Arteriosus ◽  
Ring Chromosome ◽  
Female Child ◽  
Facial Dysmorphism ◽  
Chromosome 4 ◽  
Talipes Equinovarus ◽  
Limb Deformities

A female child born preterm with intrauterine growth retardation and presenting with facial dysmorphism with clefts, microcephaly, limb deformities, and congenital abnormalities involving cardiovascular and urinary systems is described. Chromosomal analysis showed ade novo46,XX,r(4)(p15.3q35) karyotype. The clinical features of the patient were compared with the phenotypic characteristics of 17 previously reported cases with ring chromosome 4 and those with Wolf-Hirschhorn syndrome (4p-). Clinical features observed in this case are consistent with the consensus phenotype in ring chromosome 4. Patent ductus arteriosus and bilateral talipes equinovarus observed in this baby widen the phenotypic spectrum associated with ring chromosome 4.

Genomic Characterization of a Rare, de Novo Unbalanced ins(3;1)(p25.3;q21.3q23.3) in a Female Child with Multiple Congenital Anomalies

2020 ◽  
Vol 160 (10) ◽  
pp. 579-588
Author(s):  
Martha L. Ornelas-Arana ◽  
Guillermo Pérez-Garcia ◽  
Carla D. Robles-Espinoza ◽  
Martha M. Rangel-Sosa ◽  
Carolina Castaneda-Garcia ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Manifestations ◽  
Recurrence Risk ◽  
Female Child ◽  
Clinical Findings ◽  
Facial Dysmorphism ◽  
End Joining ◽  
Position Effects ◽  
Genomic Characterization

“Simple” 1-way interchromosomal insertions involving an interstitial 1q segment are rare, and therefore, their characterization at the base pair level remains understudied. Here, we describe the genomic characterization of a previously unreported de novo interchromosomal insertion (3;1) entailing an about 12-Mb pure gain of 1q21.3q23.3 that causes typical (microcephaly, developmental delay, and facial dysmorphism) and atypical (interauricular communication, small feet with bilateral deep plantar creases, syndactyly of II-IV toes, and mild pachyonychia of all toes) clinical manifestations associated with this region. Based on our analyses, we hypothesize that the duplication of a subset of morbid genes (including <i>LMNA</i>, <i>USF1</i>, <i>VANGL2</i>, <i>LOR</i>, and <i>POGZ</i>) could account for most clinical findings in our patient. Furthermore, the apparent disruption of a promoter region (between <i>CPNE9</i> and <i>BRPF1</i>) and a topologically associated domain also suggests likely pathogenic reconfiguration/position effects to contribute to the patient’s phenotype. In addition to further expanding the clinical spectrum of proximal 1q duplications and evidencing the phenotypical heterogeneity among similar carriers, our genomic findings and observations suggest that randomness – rather than lethality issues – may account for the paucity of “simple” interchromosomal insertions involving the 1q21.3q23.3 region as genomic donor and distal 3p25.3 as receptor. Moreover, the microhomology sequence found at the insertion breakpoint is consistent with a simple nonhomologous end-joining mechanism, in contrast to a chromothripsis-like event, which has previously been seen in other nonrecurrent insertions. Taken together, the data gathered in this study allowed us to inform this family about the low recurrence risk but not to predict the reproductive prognosis for hypothetical carriers. We highlight that genomic-level assessment is a powerful tool that allows the visualization of the full landscape of sporadic chromosomal injuries and can be used to improve genetic counseling.

scholarly journals Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Shan Li ◽  
Ke-wang Xi ◽  
Ting Liu ◽  
Ying Zhang ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Clinical Features ◽  
De Novo ◽  
Genetic Disorder ◽  
Deletion Syndrome ◽  
Facial Dysmorphism ◽  
Germline Mosaicism ◽  
Third Generation Sequencing ◽  
Neurological Features ◽  
Hands And Feet ◽  
Abnormal Behaviors

Abstract Background Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome. Case presentation We describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region. Conclusions Our case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.

scholarly journals Prenatal Diagnosis of 4p and 4q Subtelomeric Microdeletion in De Novo Ring Chromosome 4

2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Halit Akbas ◽  
Naci Cine ◽  
Mahmut Erdemoglu ◽  
Ahmet Engin Atay ◽  
Selda Simsek ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Critical Region ◽  
Array Cgh ◽  
De Novo ◽  
Ring Chromosome ◽  
Maternal Serum ◽  
Chromosome 4 ◽  
Maternal Serum Screening ◽  
Ring Chromosomes ◽  
Subtelomeric Deletion

Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH). However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.

scholarly journals Ring Autosomes: Some Unexpected Findings

2012 ◽  
Vol 15 (2) ◽  
pp. 35-46 ◽  
Author(s):  
L. Caba ◽  
C. Rusu ◽  
V. Plăiaşu ◽  
G. Gug ◽  
M. Grămescu ◽  
...  
Keyword(s):  
Clinical Features ◽  
De Novo ◽  
Genetic Material ◽  
Ring Chromosome ◽  
Chromosome 5 ◽  
Ring Chromosomes ◽  
Mosaic Form ◽  
Unexpected Findings

ABSTRACT Ring chromosomes are rare entities, usually associated with phenotypic abnormalities in correlation with the loss of genetic material. There are various breakpoints and sometimes there is a dynamic mosaicism that is reflected in clinical features. Most of the ring chromosomes are de novo occurrences. Our study reflects the experience of three Romanian cytogenetic laboratories in the field of ring chromosomes. We present six cases with ring chromosomes involving chromosomes 5, 13, 18, and 21. All ring chromosomes were identified after birth in children with plurimalformative syndromes. The ring chromosome was present in mosaic form in three cases, and this feature reflects the ring’s instability. In case of ring chromosome 5, we report a possible association with oculo-auriculo-vertebral spectrum.

Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations

2016 ◽  
Vol 32 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Jung Min Ko ◽  
Jae So Cho ◽  
Yongjin Yoo ◽  
Jieun Seo ◽  
Murim Choi ◽  
...  
Keyword(s):  
De Novo ◽  
Genetic Disorder ◽  
Ductus Arteriosus ◽  
Developmental Dysplasia ◽  
Facial Dysmorphism ◽  
Sequencing Analysis ◽  
Self Mutilation ◽  
Small Hands ◽  
Hands And Feet ◽  
Dysplasia Of The Hip

Wiedemann-Steiner syndrome is a rare genetic disorder characterized by short stature, hairy elbows, facial dysmorphism, and developmental delay. It can also be accompanied by musculoskeletal anomalies such as muscular hypotonia and small hands and feet. Mutations in the KMT2A gene have only recently been identified as the cause of Wiedemann-Steiner syndrome; therefore, only 16 patients from 15 families have been described, and new phenotypic features continue to be added. In this report, we describe 2 newly identified patients with Wiedemann-Steiner syndrome who presented with variable severity. One girl exhibited developmental dysplasia of the hip and fibromatosis colli accompanied by other clinical features, including facial dysmorphism, hypertrichosis, patent ductus arteriosus, growth retardation, and borderline intellectual disability. The other patient, a boy, showed severe developmental retardation with automatic self-mutilation, facial dysmorphism, and hypertrichosis at a later age. Exome sequencing analysis of these patients and their parents revealed a de novo nonsense mutation, p.Gln1978*, of KMT2A in the former, and a missense mutation, p.Gly1168Asp, in the latter, which molecularly confirmed the diagnosis of Wiedemann-Steiner syndrome.

Characterization of a de novo Supernumerary Neocentric Ring Chromosome Derived from Chromosome 7

2015 ◽  
Vol 147 (2-3) ◽  
pp. 111-117 ◽  
Author(s):  
Camille Louvrier ◽  
Grégory Egea ◽  
Audrey Labalme ◽  
Vincent Des Portes ◽  
Sophie Gazzo ◽  
...  
Keyword(s):  
Array Cgh ◽  
De Novo ◽  
Ring Chromosome ◽  
Partial Trisomy ◽  
Complete Characterization ◽  
Chromosome 7 ◽  
Oligonucleotide Array ◽  
Facial Dysmorphism ◽  
Bioinformatic Tools

Supernumerary ring chromosomes (SRC) are usually derived from regions adjacent to the centromere. Their identification may be challenging, particularly in case of low mosaicism. Here, we report on a patient who was referred for major in utero growth retardation, severe developmental delay, facial dysmorphism, cleft palate, and hypospadias. The karyotype showed a small SRC in mosaic. The combination of FISH, M-FISH and array-CGH was necessary for a complete characterization of this SRC. M-FISH revealed that the SRC originated from chromosome 7. Array-CGH performed with a 400K oligonucleotide array showed a gain in region 7q22.1q31.1 present in low mosaic. This result was confirmed by FISH using BAC probes specific for chromosome 7. The SRC was a neocentric ring derived from 7q22.1q31.1 and was found in only 8% of the cells. This is the first patient carrying a mosaic neocentric SRC derived from the long arm of chromosome 7. Our study emphasizes the need to combine different techniques and to use adapted bioinformatic tools for low-mosaicism marker identification. It also contributes to the delineation of the partial trisomy 7q phenotype.

scholarly journals Prenatal Diagnosis of a 2.5 Mb De Novo 17q24.1q24.2 Deletion Encompassing KPNA2 and PSMD12 Genes in a Fetus with Craniofacial Dysmorphism, Equinovarus Feet, and Syndactyly

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Marie-Emmanuelle Naud ◽  
Lucie Tosca ◽  
Jelena Martinovic ◽  
Julien Saada ◽  
Corinne Métay ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Prenatal Diagnosis ◽  
De Novo ◽  
Chromosomal Microarray ◽  
Facial Dysmorphism ◽  
Chromosomal Microarray Analysis ◽  
Conventional Cytogenetic Analysis ◽  
First Case ◽  
Craniofacial Dysmorphism ◽  
Talipes Equinovarus

Interstitial 17q24.1 or 17q24.2 deletions were reported after conventional cytogenetic analysis or chromosomal microarray analysis in patients presenting intellectual disability, facial dysmorphism, and/or malformations. We report on a fetus with craniofacial dysmorphism, talipes equinovarus, and syndactyly associated with a de novo 2.5 Mb 17q24.1q24.2 deletion. Among the deleted genes, KPNA2 and PSMD12 are discussed for the correlation with the fetal phenotype. This is the first case of prenatal diagnosis of 17q24.1q24.2 deletion.

ASSOCIATION OF PATENT DUCTUS ARTERIOSUS SIZE WITH CLINICAL FEATURES AND SHORT-TERM OUTCOMES IN PRETERM INFANTS LESS THAN 34 WEEKS

2020 ◽  
Vol 07 (03) ◽  
pp. 105-108
Author(s):  
Chandrakala Bada Shekharappa ◽  
Edison Albert Balakrishnan Elizabeth ◽  
Bharathi Balachander
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Clinical Features ◽  
Ductus Arteriosus ◽  
Short Term ◽  
Patent Ductus

Two Novel Cases of Autosomal Translocations in the Horse: Warmblood Family Segregating t(4;30) and a Cloned Arabian with a de novo t(12;25)

2020 ◽  
Vol 160 (11-12) ◽  
pp. 688-697
Author(s):  
Sharmila Ghosh ◽  
Candice F. Carden ◽  
Rytis Juras ◽  
Mayra N. Mendoza ◽  
Matthew J. Jevit ◽  
...  
Keyword(s):  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Congenital Abnormalities ◽  
Assisted Reproductive Technologies ◽  
De Novo ◽  
Reproductive Technologies ◽  
Balanced Translocation ◽  
Translocation Breakpoints ◽  
Normal Offspring ◽  
Embryonic Death

We report 2 novel autosomal translocations in the horse. In Case 1, a breeding stallion with a balanced t(4p;30) had produced normal foals and those with congenital abnormalities. Of his 9 phenotypically normal offspring, 4 had normal karyotypes, 4 had balanced t(4p;30), and 1 carried an unbalanced translocation with tertiary trisomy of 4p. We argue that unbalanced forms of t(4p;30) are more tolerated and result in viable congenital abnormalities, without causing embryonic death like all other known equine autosomal translocations. In Case 2, two stallions produced by somatic cell nuclear transfer from the same donor were karyotyped because of fertility issues. A balanced translocation t(12q;25) was found in one, but not in the other clone. The findings underscore the importance of routine cytogenetic screening of breeding animals and animals produced by assisted reproductive technologies. These cases will contribute to molecular studies of translocation breakpoints and their genetic consequences in the horse.

Sign in / Sign up

Export Citation Format

Share Document