scholarly journals Jacobsen syndrome and neonatal bleeding: report on two unrelated patients

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Gregorio Serra ◽  
Luigi Memo ◽  
Vincenzo Antona ◽  
Giovanni Corsello ◽  
Valentina Favero ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Comparative Genomic ◽  
Fish Analysis ◽  
Variable Degree ◽  
Jacobsen Syndrome ◽  
Contiguous Gene ◽  
Clinical Consequences ◽  
11Q Deletion

Abstract Introduction In 1973, Petrea Jacobsen described the first patient showing dysmorphic features, developmental delay and congenital heart disease (atrial and ventricular septal defect) associated to a 11q deletion, inherited from the father. Since then, more than 200 patients have been reported, and the chromosomal critical region responsible for this contiguous gene disorder has been identified. Patients’ presentation We report on two unrelated newborns observed in Italy affected by Jacobsen syndrome (JBS, also known as 11q23 deletion). Both patients presented prenatal and postnatal bleeding, growth and developmental delay, craniofacial dysmorphisms, multiple congenital anomalies, and pancytopenia of variable degree. Array comparative genomic hybridization (aCGH) identified a terminal deletion at 11q24.1-q25 of 12.5 Mb and 11 Mb, in Patient 1 and 2, respectively. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletion for Patient 1; parents of Patient 2 refused further genetic investigations. Conclusions Present newborns show the full phenotype of JBS including thrombocytopenia, according to their wide 11q deletion size. Bleeding was particularly severe in one of them, leading to a cerebral hemorrhage. Our report highlights the relevance of early diagnosis, genetic counselling and careful management and follow-up of JBS patients, which may avoid severe clinical consequences and lower the mortality risk. It may provide further insights and a better characterization of JBS, suggesting new elements of the genotype-phenotype correlations.

Clinical and Cytogenomic Characterization of De Novo 11p14.3-p15.5 Duplication Associated with 18q23 Deletion in an Egyptian Female Infant

2020 ◽  
Author(s):  
Hanan H. Afifi ◽  
Ghada Y. El-Kamah ◽  
Alaa K. Kamel ◽  
Sally G. Abd Allah ◽  
Sayda Hammad ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Ductus Arteriosus ◽  
Chromosomal Rearrangements ◽  
Clinical Manifestations ◽  
Brain Magnetic Resonance Imaging ◽  
Comparative Genomic ◽  
Septal Hypertrophy

AbstractPaternal microduplication of 11p14.3-p15.5 causes the clinical manifestations of Beckwith–Wiedemann syndrome (BWS), while microdeletion of 18q23-ter is clinically characterized by short stature, congenital malformations, and developmental delay. We describe a 15-month-old girl presenting with protruding tongue, dysmorphic facial features, moderate developmental delay, umbilical hernia, hypotonia, mild-to-moderate pulmonary hypertension, small patent ductus arteriosus, and mild ventricular septal hypertrophy. Brain magnetic resonance imaging showed mild atrophic changes. Chromosomal analysis revealed 46, XX, add(18)(q23). Fluorescence in situ hybridization using subtelomere 18q and whole chromosome painting 18 showed subtelomere deletion in 18q, and the add segment was not derived from chromosome 18. Microarray-based comparative genomic hybridization detected a 22 Mb duplication of chromosome 11p15.5p14.3 and a 3.7 Mb deletion of chromosome 18q23. The phenotype of the chromosomal rearrangements is probably resulted from a combination of dosage-sensitive genes. Our patient had clinical manifestations of both 18q deletion and BWS.

scholarly journals Cerebral White Matter Lesions and Dysmorphisms: Signs Suggestive of 6p25 Deletion Syndrome—Literature Review

2019 ◽  
Vol 08 (04) ◽  
pp. 205-211
Author(s):  
Piero Pavone ◽  
Simona Domenica Marino ◽  
Giovanni Corsello ◽  
Martino Ruggieri ◽  
Danilo Castellano Chiodo ◽  
...  
Keyword(s):  
White Matter ◽  
Developmental Delay ◽  
De Novo ◽  
Clinical Manifestations ◽  
Deletion Syndrome ◽  
Cerebral White Matter ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Perivascular Spaces ◽  
Renal Malformations

AbstractDeletion of the region including chromosome 6p25 has been defined as a syndrome, with more than 68 reported cases. Individuals affected by the syndrome exhibit variable findings, including developmental delay and intellectual disability, cardiac anomalies, dysmorphic features, and—less commonly—skeletal and renal malformations. Ocular and hearing abnormalities are the most notable presenting features. The region encompasses more than 15 genes, of which the FOX group is the most likely causal factor of the clinical manifestations. We report the case of a 2-year-old child with developmental delay, generalized hypotonia, facial dysmorphism, and anomalies involving malformations of the eyes, heart, teeth, and skeleton. The magnetic resonance imaging (MRI) of the child's brain displayed cerebral anomalies involving the white matter, perivascular spaces, and corpus callosum. Array-CGH (comparative genomic hybridization) analysis displayed a de novo partial deletion of the short arm of chromosome 6, extending 5.13 Mb from nt 407.231 to nt 5.541.179. In infancy, neuroradiologic findings of abnormalities in the cerebral white matter and other neurologic anomalies elsewhere in the brain, in association with dysmorphisms and malformations, are highly suggestive of the diagnosis of 6p25 deletion syndrome. When these anomalies are found, the syndrome must be included in the differential diagnosis of disorders affecting the cerebral white matter.

scholarly journals NF1 microdeletion syndrome: case report of two new patients

2019 ◽  
Vol 45 (1) ◽  
Author(s):  
Gregorio Serra ◽  
Vincenzo Antona ◽  
Giovanni Corsello ◽  
Federico Zara ◽  
Ettore Piro ◽  
...  
Keyword(s):  
De Novo ◽  
Present Report ◽  
Pulmonary Stenosis ◽  
Gene Array ◽  
Brain Magnetic Resonance Imaging ◽  
Comparative Genomic ◽  
Fish Analysis ◽  
Heterozygous Deletion ◽  
Microdeletion Syndrome ◽  
Molecular Features

Abstract Background 17q11.2 microdeletions, which include the neurofibromatosis type 1 (NF1) gene region, are responsible for the NF1 microdeletion syndrome, observed in 4.2% of all NF1 patients. Large deletions of the NF1 gene and its flanking regions are associated with a more severe NF1 phenotype than the NF1 general population. Case presentation We hereby describe the clinical and molecular features of two girls (aged 2 and 4 years, respectively), with non-mosaic atypical deletions. Patient 1 showed fifteen café-au-lait spots and axillary freckling, as well as a Lisch nodule in the left eye, strabismus, high-arched palate, malocclusion, severe kyphoscoliosis, bilateral calcaneovalgus foot, mild generalized hypotonia, hyperactivity and deficits of speech-related abilities. NF1 genomic rearrangements through multiplex ligation-dependent probe amplification (MLPA) detected an heterozygous deletion of the whole NF1 gene. Array comparative genomic hybridization (a-CGH) analysis defined a 17q11.2 deletion of about 1 Mb (breakpoints at positions 29,124,299 and 30,151,654), which involved different genes (partially CRLF3, ATAD5, TEFM, ADAP2, RNF135, OMG, EVI2B, EVI2A, RAB11FIP4), including NF1. Patient 2 showed growth and developmental delay, supravalvular pulmonary stenosis, twenty-five café-au-lait spots, axillary freckling, craniofacial dysmorphic features, short neck with pterygium, limb abnormalities and foci of neural dysplasia on brain magnetic resonance imaging (MRI). MLPA detected an heterozygous deletion of NF1, which was detailed by a-CGH indicating the positions 29,124,299 and 30,326,958 as its breakpoints, and which included aside from the genes deleted in Patient 1 also COPRS, UTP6 and partially SUZ12. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletions in both cases. Conclusions The present report will likely provide further insights and a better characterization of NF1 microdeletion syndrome.

Comparison of genomic abnormality in malignant mesothelioma by the site of origin

2014 ◽  
Vol 67 (12) ◽  
pp. 1038-1043 ◽  
Author(s):  
Maiko Takeda ◽  
Takahiko Kasai ◽  
Yasunori Enomoto ◽  
Masato Takano ◽  
Kohei Morita ◽  
...  
Keyword(s):  
Malignant Mesothelioma ◽  
In Situ Hybridisation ◽  
Homozygous Deletion ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Fish Analysis ◽  
Fluorescence In Situ Hybridisation ◽  
Hybridisation Analysis ◽  
Genetic Events

AimsMalignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes are losses in 9p21, 1p36, 22q12 and 14q32, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. We have examined various genomic losses and gains in MM and benign mesothelial proliferation by fluorescence in situ hybridisation (FISH) analysis. 9p21 deletion was reported to be less frequent in peritoneal than in pleural MMs. This study analysed various genomic losses and gains in MM by the site of origin using FISH analysis.Materials and methodsWe performed FISH analysis using paraffin-embedded tissues from 54 cases (40 pleural and 14 peritoneal) of MMs and compared the frequency of genomic abnormality by the site of origin.Results9p21 deletion was shown in 34 of 40 cases (85%) of pleural MMs, and was less frequent in five of 14 cases (36%) of peritoneal MMs (p<0.001) by FISH analysis. By contrast, 5p15 and 7p12 amplification was more significantly frequent in peritoneal than in pleural MMs. No difference between the two sites of MM in other genes was found.Conclusions9p21 homozygous deletion assessed by FISH has been reported to be useful for differentiating MM from reactive mesothelial proliferation, but it should be noted that 9p21 deletion was less frequent in peritoneal MM. Our study suggests that the pathway of the genetic abnormality might vary between pleural and peritoneal MM.

scholarly journals A 9-year-old-girl with Phelan McDermid Syndrome, who had been diagnosed with an autism spectrum disorder

2016 ◽  
Vol 19 (2) ◽  
pp. 85-90 ◽  
Author(s):  
I Görker ◽  
H Gürkan ◽  
S Demir Ulusal ◽  
E Atlı ◽  
E Ikbal Atlı
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Comparative Genomic ◽  
Parental Origin ◽  
Mild Intellectual Disability ◽  
First Case

AbstractPhelan McDermid Syndrome (PHMDS) (OMIM #606232), is a contiguous gene disorder resulting from deletion of the distal long arm of chromosome 22. The 22q13.3 deletions and mutations that lead to a loss of a functional copy of SHANK3 (OMIM *606230) cause the syndrome, characterized by moderate to profound intellectual disability, severely delayed or absent speech, hypotonia, and autism spectrum disorder (ASD) or ASD traits. In this study, we present the case of a 9-year-old girl who had earlier been diagnosed with an ASD. Our findings were a clinically mild intellectual disability, rounded face, pointed chin but no autistic findings. We learned that her neuromotor development was delayed and she had neonatal hypotonia in her history. A heterozygous deletion of MLC1, SBF1, MAPK8IP2, ARSA, SHANK3 and ACR genes, located on 22q13.33, was defined by multiplex ligation-dependent probe amplification (MLPA). Deletion of 22q13.3 (ARSA) region was confirmed by a fluorescent in situ hybridization (FISH) technique. The 22q13.3 deletion was found to be de novo in our patient, and she was diagnosed with PHMDS. We confirmed the 22q13.3 deletion and also determined a gain of 8p23.3-23.2 by array comparative genomic hybridization (aCGH). Fluorescent in situ hybridization was performed to determine whether the deletion was of parental origin and to identify regions of chromosomes where the extra 8p may have been located. The parents were found to be normal. The extra copy of 8p was observed on 22q in the patient. She is the first case reported in association with the 22q deletion of 8p duplications in the literature.

scholarly journals Genotype-Phenotype Characterization of Wolf-Hirschhorn Syndrome Confirmed by FISH: Case Reports

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
F. Sheth ◽  
O. R. Akinde ◽  
C. Datar ◽  
O. V. Adeteye ◽  
J. Sheth
Keyword(s):  
Cytogenetic Study ◽  
Case Reports ◽  
Normal Karyotype ◽  
Comparative Genomic ◽  
Molecular Cytogenetic ◽  
Contiguous Gene ◽  
Multiple Malformation ◽  
Molecular Cytogenetic Techniques

The Wolf-Hirschhorn syndrome (WHS) is a multiple malformation and contiguous gene syndrome resulting from the deletion encompassing a 4p16.3 region. A microscopically visible terminal deletion on chromosome 4p (4p16→pter) was detected in Case 1 with full blown features of WHS. The second case which had an interstitial microdeletion encompassingWHSC 1andWHSC 2genes at 4p16.3 presented with less striking clinical features of WHS and had an apparently “normal” karyotype. The severity of the clinical presentation was as a result of haploinsufficiency and interaction with surrounding genes as well as mutations in modifier genes located outside the WHSCR regions. The study emphasized that an individual with a strong clinical suspicion of chromosomal abnormality and a normal conventional cytogenetic study should be further investigated using molecular cytogenetic techniques such as fluorescencein situhybridization (FISH) or array-comparative genomic hybridization (a-CGH).

scholarly journals Mosaic Intrachromosomal Triplication of (12)(p11.2p13) in a Patient with Pallister-Killian Syndrome

2012 ◽  
Vol 15 (1) ◽  
pp. 61-64 ◽  
Author(s):  
S Yakut ◽  
E Mıhcı ◽  
Clark Altiok ◽  
Z Cetin ◽  
I Keser ◽  
...  
Keyword(s):  
Chromosomal Abnormality ◽  
De Novo ◽  
Genetic Disorder ◽  
Chromosome 12 ◽  
Fish Analysis ◽  
Fibroblast Cells ◽  
The Third ◽  
Isochromosome 12P ◽  
Conventional Cytogenetics

Mosaic Intrachromosomal Triplication of (12)(p11.2p13) in a Patient with Pallister-Killian SyndromePallister-Killian syndrome (PKS) is a rare genetic disorder usually characterized by mosaic tetrasomy of isochromosome 12p detected in cultured fibroblast cells. We describe here a patient with PKS and intrachromosomal triplication of the short arm of chromosome 12. Her karyo-type was mos 46, XX, inv trp(12)(p11.2p13)[34]/46, XX[16] de novo by conventional cytogenetics and fluorescent in situ hybridization (FISH) analysis. However, this chromosomal abnormality was not detected from the patient's cultured blood lymphocytes. We report here the third patient with intrachromosomal triplication on the short arm of chromosome 12, presenting a PKS phenotype.

scholarly journals De Novo Interstitial Deletion of 9q in a Pediatric Patient With Global Developmental Delay

2019 ◽  
Vol 6 ◽  
pp. 2329048X1984492
Author(s):  
Dennis Keselman ◽  
Ram Singh ◽  
Ninette Cohen ◽  
Zipora Fefer
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Snp Array ◽  
Interstitial Deletion ◽  
Global Developmental Delay ◽  
Comparative Genomic ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Basal Cell Nevus Syndrome ◽  
Ptch1 Gene

Cytogenomic microarray (CMA) methodologies, including array comparative genomic hybridization (aCGH) and single-nucleotide polymorphism-detecting arrays (SNP-array), are recommended as the first-tier test for the evaluation of imbalances associated with intellectual disability, autism, and multiple congenital anomalies. The authors report on a child with global developmental delay (GDD) and a de novo interstitial 7.0 Mb deletion of 9q21.33q22.31 detected by aCGH. The patient that the authors report here is noteworthy in that she presented with GDD and her interstitial deletion is not inclusive of the 9q22.32 locus that includes the PTCH1 gene, which is implicated in Gorlin syndrome, or basal cell nevus syndrome (BCNS), has not been previously reported among patients with a similar or smaller size of the deletion in this locus suggesting that the genomic contents in the identified deletion on 9q21.33q22.31 is critical for the phenotype.

scholarly journals De Novo Subtelomeric 6p25.3 Deletion with Duplication of 6q23.3-q27: Genotype–Phenotype Correlation

2019 ◽  
Vol 09 (01) ◽  
pp. 032-039
Author(s):  
Emine Ikbal Atli ◽  
Hakan Gurkan ◽  
Engin Atli ◽  
Ulfet Vatansever ◽  
Betul Acunas ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Signs ◽  
Chromosome Analysis ◽  
Clinical Syndrome ◽  
Chromosome Band ◽  
Medium Size ◽  
Comparative Genomic ◽  
Chromosome 6 ◽  
First Case

AbstractDuplications of 6q and deletions of 6p have been reported in more than 30 cases of live born infants and given rise to widespread abnormalities recognizable as a specific clinical syndrome. Different phenotypes have been described with variable clinical signs. Most cases involve the coexistence of unbalanced translocations affecting one or the other of the chromosomes. However, duplication of both chromosome 6q and deletion of 6p regions have been reported in only a few cases. Here, we report the first duplication of chromosome band 6q23.3–q27 with deletion of 6p25.3. This is the first case in the literature involving changes to these specific chromosomal regions; a medium size duplication of the distal long arm and smaller deletion of the terminal short arm of chromosome 6. In the literature, there are no other cases where these two specific chromosomal aberrations are observed together. Conventional chromosome analysis was performed to investigate the patient. Chromosome structure was identified using fluorescence in situ hybridization for subtelomeric regions of chromosome 6 and array comparative genomic hybridization analysis (array-CGH).

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