scholarly journals A new case of intragenic deletion of the TCF4 gene without features of Pitt-Hopkins syndrome

2020 ◽  
Vol 3 (2) ◽  
pp. 56-58
Author(s):  
Leona Morozin Pohovski ◽  
Adriana Bobinec ◽  
Ana-Maria Measic ◽  
Ivona Sansovic ◽  
Ingeborg Barisic
Keyword(s):  
Genetic Disorder ◽  
Protein Isoforms ◽  
Comparative Genomic ◽  
Bhlh Transcription Factor ◽  
Balanced Translocation ◽  
Genomic Alterations ◽  
Coding Sequence ◽  
Psychomotor Delay ◽  
Severe Intellectual Disability ◽  
First Case

Different genomic alterations affecting the TCF4 gene are usually associated with Pitt-Hopkins syndrome (PTHS). This syndrome is a rare neurodevelopmental genetic disorder characterized by distinctive facial features, abnormal breathing, psychomotor delay and severe intellectual disability (ID). The genomic alterations include whole or partial gene deletion; balanced translocation disrupting the coding sequence of the gene; and intragenic variants. The TCF4 gene encodes a basic helix-loop-helix (bHLH) transcription factor 4. Using alternative promoters, TCF4 can be transcribed from a number of alternative initial exons, allowing for translation of variable protein isoforms containing different functional domains. Full-length TCF4 has two activation domains (AD1 and AD2) that are thought to modulate transcriptional activity, a NLS domain (nuclear localization signal) that controls subcellular localization and bHLH domain. Typical PTHS patients have aberration localized between exons 9 and 18 of the gene. On the other hand, variants affecting the first protein coding exons give rise to mild non-syndromic ID. We present a ten-year-old girl with psychomotor delay and mild ID without the typical features of PTHS. Genetic investigation using array-based comparative genomic hybridization, revealed a 73.45 kb deletion within the TCF4 gene. The deletion encompassing only exon 6 (NM_001083962). This deletion was not detected in both parents. Cytogenetic analysis excluded balanced translocation disrupting the coding sequence of the gene. To the best of our knowledge, this is the first case described in literature involving only exon 6. The findings in our patients support the notion that position of the alteration in TCF4 is relevant to the phenotype. Reporting our case we want to contribute to the phenotype-genotype correlation in patients with intragenomic deletion of TCF4 gene.

scholarly journals Distal Deletion of Chromosome 11q Encompassing Jacobsen Syndrome without Platelet Abnormality

2014 ◽  
Vol 8 ◽  
pp. CMPed.S18121
Author(s):  
Frenny J. Sheth ◽  
Chaitanya Datar ◽  
Joris Andrieux ◽  
Anand Pandit ◽  
Darshana Nayak ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Large Deletion ◽  
Comparative Genomic ◽  
Chromosome 11 ◽  
Balanced Translocation ◽  
Facial Profile ◽  
Aberrant Chromosome ◽  
Jacobsen Syndrome ◽  
Normal Father ◽  
11Q Deletion

Terminal 11q deletion, known as Jacobsen syndrome (JBS), is a rare genetic disorder associated with numerous dysmorphic features. We studied two cases with multiple congenital anomalies that were cytogenetically detected with deletions on 11q encompassing JBS region: 46,XX,der(11) del(11)(q24). Array comparative genomic hybridization (aCGH) analysis confirmed partial deletion of 11.8–11.9 Mb at 11q24.1q25 (case 1) and 13.9–14 Mb deletion at 11q23.3q25 together with 7.3–7.6 Mb duplication at 12q24.32q24.33 (case 2). Dysmorphism because of the partial duplication of 12q was not overtly decipherable over the Jacobsen phenotype except for a triangular facial profile. Aberrant chromosome 11 was inherited from phenotypically normal father, carrier of balanced translocation 46,XY,t(11;12)(q23.3; q24.32). In the present study, both cases had phenotypes that were milder than the ones described in literature despite having large deletion size. Most prominent features in classical JBS is thrombocytopenia, which was absent in both these cases. Therefore, detailed functional analysis of terminal 11q region is warranted to elucidate etiology of JBS and their clinical presentation.

Anesthesia in Carvajal syndrome; the first case report

2020 ◽  
Vol 24 (1) ◽  
pp. 105-107
Author(s):  
Sedighe Shahhosseini ◽  
Reza Aminnejad ◽  
Amir Shafa ◽  
Mehrdad Memarzade
Keyword(s):  
Intensive Care ◽  
Case Report ◽  
Surgical Resection ◽  
Genetic Disorder ◽  
Anesthetic Technique ◽  
Close Monitoring ◽  
Anesthesia Management ◽  
Rare Genetic Disorder ◽  
First Case ◽  
Anesthetic Considerations

Carvajal syndrome is a rare genetic disorder. Patients reporting for surgery pose some difficulties in anesthesia management. In this case report we present the case of a 12-year-old boy, who was a known case of Carvajal syndrome, referred for surgical resection of perianal condyloma. Close monitoring of hemodynamic status is the mainstay of anesthetic considerations in such patients. As in any other challenging scenario, it should be kept in mind that ‘there is no safest anesthetic agent, nor the safest anesthetic technique; there is only the safest anesthesiologist’. Citation: Shahhosseini S, Aminnejad R, Shafa A, Memarzadeh M. Anesthesia in Carvajal syndrome; the first case report. Anaesth pain intensive care 2020;24(1):___ DOI: https://doi.org/10.35975/apic.v24i1.

scholarly journals A case report and mechanism analysis of a normal phenotype mosaic 47, XXY complicated by paternal iUPD (9) who had a normal PGD result

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Dan Li ◽  
Yun Wang ◽  
Nan Zhao ◽  
Liang Chang ◽  
Ping Liu ◽  
...  
Keyword(s):  
Case Report ◽  
Karyotype Analysis ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Comparative Genomic ◽  
Klinefelter’S Syndrome ◽  
Mechanism Analysis ◽  
Klinefelter's Syndrome ◽  
Preimplantation Genetic Testing ◽  
First Case

Abstract Background Uniparental disomy (UPD) refers to the situation in which two copies of homologous chromosomes or part of a chromosome originate from the one parent and no copy is supplied by the other parent. Case presentation Here, we reported a woman whose karyotype was 46, XX, t (1;17)(q42;q21), has obtained 5 embryos by intracytoplasmic sperm injection (ICSI) after one cycle of in vitro fertility (IVF). After microarray-based comparative genomic hybridization (array-CGH) for preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR), two embryos were balanced, one balanced embryo was implanted and the patient successfully achieved pregnancy. Amniocentesis was performed at the 19th week of gestation for karyotype analysis and single nucleotide polymorphism (SNP)-array test. The result of karyotype analysis was: mos 47, XXY [19]/46, XY [81]; SNP-array results revealed 46, XY, iUPD (9) pat. After full genetic counseling for mosaic Klinefelter’s syndrome and paternal iUPD (9), the couple decided to continue pregnancy, and the patient gave birth to a healthy boy. The newborn is now 3.5 years old, and developed normally. This case will provide counseling evidences of paternal iUPD (9) for doctors. Conclusions This is the first case report of paternal iUPD9 with mosaic Klinefelter’s syndrome, and no abnormality has been observed during the 3.5-year follow-up. Further observation is required to determine whether the imprinted genes on the chromosomes are pathogenic and whether recessive pathogenetic genes are activated.

scholarly journals Van Buchem Disease: First Case Report from the Indian Subcontinent with an Early Presentation

2021 ◽  
Vol 11 (01) ◽  
pp. e38-e41
Author(s):  
Saurabh Maheshwari ◽  
Sonam Yangzom ◽  
K. Uday Bhanu ◽  
Uddandam Rajesh ◽  
Ashok Narayan
Keyword(s):  
Western Europe ◽  
Indian Subcontinent ◽  
Genetic Disorder ◽  
Rare Condition ◽  
Bone Dysplasia ◽  
Feedback Mechanism ◽  
Early Presentation ◽  
First Case ◽  
Cranial Nerve Palsies ◽  
Van Buchem Disease

AbstractVan Buchem disease is a rare autosomal recessive genetic disorder that causes a compromised inhibitory feedback mechanism resulting in increased bone formation and overgrowth of the skeleton leading to a variety of neurological symptoms. It has been reported in less than 50 patients most of which were in western Europe. We report the first case of this condition from the Indian subcontinent with an early presentation. This patient presented with a global delay in attaining the developmental milestones and progressive reduction in visual acuity and loss of hearing. He had dysmorphic facies, multiple cranial nerve palsies, and severe visual and auditory deficits. Imaging revealed sclerosing bone dysplasia. This case illustrates the clinical and imaging findings of this rare condition.

Exclusive Neurogenic Bladder and Fecal Incontinency in an Achondroplasic Child Successfully Treated with Lumbar Foraminal Decompression

2021 ◽  
pp. 1-6
Author(s):  
Flavio Giordano ◽  
Matteo Lenge ◽  
Pierarturo Donati ◽  
Lorenzo Mongardi ◽  
Gianpiero Di Giacomo ◽  
...  
Keyword(s):  
Fecal Incontinence ◽  
Neurogenic Bladder ◽  
Genetic Disorder ◽  
Motor Impairment ◽  
Foramen Magnum ◽  
Clinical Findings ◽  
Lumbar Stenosis ◽  
Endochondral Bone ◽  
Case Presentation ◽  
First Case

<b><i>Introduction:</i></b> Achondroplasia is a genetic disorder characterized by defects in the development of endochondral bone resulting in skeletal abnormalities like stenosis of the foramen magnum and of the spine, shortened limb bones, and macrocephaly. Congenital spinal stenosis is frequent and due to premature fusion of the pedicles to the laminae. <b><i>Case Presentation:</i></b> We report a case of neurogenic bladder and fecal incontinence due to lumbar stenosis successfully treated with L1–L5 partial laminectomy and foraminotomy in a 7-year-old achondroplasic child. <b><i>Discussion/Conclusion:</i></b> To our knowledge, this is the first case report of exclusive neurogenic bladder and fecal incontinence in an achondroplasic child. Neurogenic bladder and fecal incontinence without motor impairment may be early and exclusive clinical findings of lumbar stenosis in children with achondroplasia.

scholarly journals Case Report: Recurrent Variant c.298 TA in CCN6 Gene Found in Progressive Pseudorheumatoid Dysplasia Patients From Patni Community of Gujarat: A Report of Three Cases

2021 ◽  
Vol 12 ◽  
Author(s):  
Harsh Sheth ◽  
Jhanvi Shah ◽  
Aadhira Nair ◽  
Premal Naik ◽  
Jayesh Sheth
Keyword(s):  
Genetic Disorder ◽  
Case Series ◽  
Missense Variant ◽  
Community Analysis ◽  
Gait Disturbance ◽  
Mutant Genotype ◽  
Progressive Pseudorheumatoid Dysplasia ◽  
First Case ◽  
Abnormal Posture ◽  
Biallelic Mutations

Biallelic mutations in the CCN6 gene are known to cause a rare genetic disorder—progressive pseudorheumatoid dysplasia (PPD). PPD is characterized by distinct joint deformities of interphalangeal joints, stiffness, gait disturbance, abnormal posture, and absence of inflammation, resulting in significant morbidity. The largest case series of PPD from India suggests c.233G&gt;A and c.1010G&gt;A to be the most common mutations in the CCN6 gene, although the distribution of these variants among endogamous communities in India has not been carried out. We here report three cases of PPD from three independent families belonging to the Patni community of Gujarat, a community known to practice endogamy. All three cases had short stature, gait disturbance, scoliosis, and interphalangeal joint deformities. Analysis by whole-exome sequencing in the first case showed the presence of a previously known, homozygous, missense variant c.298T&gt;A (p.Cys100Ser) in exon 3 of the CCN6 gene in all cases. Due to all three families belonging to the same community, analysis by Sanger sequencing in the remaining two cases for the variant mentioned earlier showed both cases to be of homozygous mutant genotype. Unaffected family members, i.e., parents and siblings, were either heterozygous carriers or wildtype for the said variant. The present case series is the first report of a recurrent variant occurring across multiple PPD-affected individuals from unrelated families belonging to the same community from India.

Genomic characterisation of multiple myeloma: study of a Portuguese cohort

2021 ◽  
pp. jclinpath-2020-207204
Author(s):  
Alexandra Couto Oliveira ◽  
Ilda Patrícia Ribeiro ◽  
Luís Miguel Pires ◽  
Ana Cristina Gonçalves ◽  
Artur Paiva ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Prognostic Value ◽  
Clinical Presentation ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Genomic Alterations ◽  
Genomic Complexity ◽  
Genome Wide ◽  
Trisomy 9

Multiple myeloma (MM) genomic complexity reflects in the variable patients’ clinical presentation. Genome-wide studies seem to be a reasonable alternative to identify critical genomic lesions. In the current study, we have performed the genomic characterisation of a Portuguese cohort of patients with MM by array comparative genomic hybridisation. Overall, the most frequently detected alterations were 13q deletions, gains of 1q, 19p, 15q, 5p and 7p and trisomy 9. Even though some identified genomic alterations were previously associated with a prognostic value, other abnormalities remain with unknown, but putative significance for patients’ clinical practice. These genomic alterations should be further assessed as possible biomarkers.

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