scholarly journals A Homozygous Synonymous Variant Likely Cause of Severe Ciliopathy Phenotype

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 945
Author(s):  
Gulten Tuncel ◽  
Bahar Kaymakamzade ◽  
Yeliz Engindereli ◽  
Sehime G. Temel ◽  
Mahmut Cerkez Ergoren
Keyword(s):  
Molecular Genetic ◽  
Coiled Coil ◽  
Renal Cysts ◽  
Joubert Syndrome ◽  
Molecular Genetic Analysis ◽  
Clinical Findings ◽  
Breathing Patterns ◽  
Compulsive Disorder ◽  
Neurodevelopmental Disease ◽  
Truncal Ataxia

Joubert syndrome (OMIM #213300) is a rare neurodevelopmental disease characterized by abnormal breathing patterns, intellectual impairment, ocular findings, renal cysts, and hepatic fibrosis. It is classified as a ciliopathy disease, where cilia function or structure in various organs are affected. Here, we report a 17-year-old male whose main clinical findings are oculomotor apraxia and truncal ataxia. Magnetic resonance imaging revealed the characteristic molar tooth sign of Joubert syndrome. He also has obsessive–compulsive disorder concomitantly, which is not a known feature of Joubert syndrome. Molecular genetic analysis revealed a homozygous c.2106G>A (p.(Thr702=)) variation in the Abelson helper integration 1 (AHI1) gene and another homozygous c.1739C>T (p.Thr580Ile) variation in the coiled-coil and C2 domain-containing protein 1A (CC2D1A) gene. Even though certain AHI1 variations were previously associated with Joubert syndrome (JS), c.2106G>A (p.(Thr702=)) was only reported in one patient in trans with another known pathogenic JS variant. The CC2D1A c.1739C>T (p.Thr580Ile) variation, on the other hand, has been reported to cause autosomal recessive nonsyndromic mental retardation, but there are conflicting interpretations about its pathogenicity. Overall, to our knowledge, this is the first patient representing a severe ciliopathy phenotype caused by a homozygous synonymous AHI1 variation. Further investigations should be performed to determine any involvement of the CC2D1A gene in ciliopathy phenotypes such as Joubert syndrome.

Fetal Beckwith-Wiedemann syndrome associated with abnormal quad test, placental mesenchymal dysplasia and HELLP syndrome

2021 ◽  
Vol 14 (6) ◽  
pp. e243415
Author(s):  
Phudit Jatavan ◽  
Theera Tongsong ◽  
Kuntharee Traisrisilp
Keyword(s):  
Genetic Analysis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Clinical Findings ◽  
Serum Biomarkers ◽  
Provisional Diagnosis ◽  
Unique Case ◽  
Clinical Criteria ◽  
Placental Mesenchymal Dysplasia

We describe a unique case of Beckwith-Wiedemann syndrome (BWS). A 29-year-old woman with ultrasound and clinical findings, specific to BWS is described. Important insights gained from this study are as follows: (1) quad test may be very useful to increase awareness of BWS. This is the first report, which demonstrated that elevated inhibin-A is related to BWS. Unexplained elevation of serum biomarkers, especially all the four markers, should raise awareness of BWS. (2) Early provisional diagnosis in this case was based on the findings of omphalocele, placental mesenchymal dysplasia and abnormal quad test. (3) Follow-up scans are important for late-occurring supportive findings, such as macroglossia, ear abnormalities and visceromegaly. (4) BWS is strongly associated with preeclampsia, which tended to be more severe and of earlier-onset. (5) Molecular genetic analysis is helpful, but not always necessary in cases of fulfilment of clinical criteria like in this case.

scholarly journals Molecular genetic analysis of 30 families with Joubert syndrome

2016 ◽  
Vol 90 (6) ◽  
pp. 526-535 ◽  
Author(s):  
T. Suzuki ◽  
N. Miyake ◽  
Y. Tsurusaki ◽  
N. Okamoto ◽  
A. Alkindy ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Molecular Genetic ◽  
Joubert Syndrome ◽  
Molecular Genetic Analysis

Novel TSC1 mutation associated with variable phenotypes in tuberous sclerosis

2013 ◽  
Vol 154 (23) ◽  
pp. 914-918 ◽  
Author(s):  
Erzsébet Kövesdi ◽  
Kinga Hadzsiev ◽  
Katalin Komlósi ◽  
Mária Kassay ◽  
Péter Barsi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
De Novo ◽  
Phenotypic Variability ◽  
Molecular Genetic ◽  
Clinical Signs ◽  
Renal Cysts ◽  
Molecular Genetic Analysis ◽  
Autosomal Dominant Disorder ◽  
Modifying Factors ◽  
Tsc1 Gene

Tuberous sclerosis is an autosomal dominant disorder, caused by mutations of the TSC1 or TSC2 genes resulting in tumor predisposition. Clinical signs include non-malignant brain tumors, skin, eye, heart and kidney abnormalities. The authors report a Hungarian family with broad phenotypic variability. First, the 5-year-old boy, showing the most symptoms was examined, whose first seizure occurred at 15 months and a cranial magnetic resonance imaging revealed numerous intracerebral calcareous foci. Except of hypopigmented skin spots, no other abnormality was found on physical examination. The mother was completely asymptomatic. Epilepsy of the maternal uncle started at the age of 3 years, of his sister at the age of 17 years and of the maternal grandmother at the age of 39 years. At the age of 52 years the grandmother developed renal cysts. Molecular genetic analysis of the family confirmed a de novo heterozygous point mutation (c.2523 C\>T) in exon 20 of the TSC1 gene. The mutation was detected in all examined family members. Despite increasing data on the pathomechanism of tuberous sclerosis, there is still little known about the genetic modifying factors influencing the broad intra- and interfamilial phenotypic variability. Orv. Hetil., 2013, 154, 914–918.

scholarly journals Molecular Genetic Cause of Achromatopsia in Two Patients of Czech Origin

2019 ◽  
Vol 75 (5) ◽  
pp. 272-276
Author(s):  
Lucia Hlavatá ◽  
Ľubica Ďuďáková ◽  
Jana Moravíková ◽  
Anna Zobanová ◽  
Bohdan Kousal ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Structural Changes ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Molecular Genetic Analysis ◽  
Clinical Findings ◽  
Gene Therapies ◽  
Pathogenic Variants ◽  
The Right ◽  
First Time

Introduction: Achromatopsia is an autosomal recessive retinal disorder with an estimated prevalence ranging from 1 in 30.000 to 50.000. The disease is caused by mutations in six different genes. The aim of the study was to perform molecular genetic analysis in 11 unrelated probands with a clinical diagnosis of achromatopsia and to describe clinical findings in those that were found to carry biallelic pathogenic mutations. Methods: All probands and their parents underwent ophthalmic examination. Mutation detection was performed using Sanger sequencing of CNGB3 exons 6, 7, 9-13, which have been found to harbour most diseasecausing mutations in patients with achromatopsia of European origin. Results: Three known pathogenic variants in CNGB3 were identified in 2 probands. Proband 1 was a compound heterozygote for the c.819_826del; p.(Arg274Valfs*13) and c.1006G>T; p.(Glu336*). Proband 2 carried the c.1148del; p.(Thr383Ilefs*13) in a homozygous state. The best corrected visual acuity in proband 1 (aged 19 years) was 0.1 in both eyes, in proband 2 (aged 8 years) 0.05 in the right eye and 0.1 in the left eye. Both individuals had nystagmus, photophobia, and absence of colour discrimination. Fundus examination appeared normal however spectral-domain optical coherence tomography revealed subtle bilaterally symmetrical structural changes in the fovea. Conclusion: Molecular genetic analysis of Czech patients with achromatopsia was performed for the first time. Identification of diseasecausing mutations in achromatopsia is important for establishing an early diagnosis, participation in clinical trials assessing gene therapies and may be also used for preimplantation genetic diagnosis.

scholarly journals Joubert Syndrome with Orofacial Digital Features

2018 ◽  
Vol 09 (01) ◽  
pp. 152-154 ◽  
Author(s):  
Parveen Bhardwaj ◽  
Minoo Sharma ◽  
Karan Ahluwalia
Keyword(s):  
Mental Retardation ◽  
Hepatic Fibrosis ◽  
Autosomal Recessive ◽  
Renal Cysts ◽  
Joubert Syndrome ◽  
Clinical Findings ◽  
Cerebellar Vermis ◽  
Radiological Findings ◽  
Ocular Abnormalities

ABSTRACTJoubert syndrome (JS) is an autosomal recessive inherited disorder characterized by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g., pigmentary retinopathy, oculomotor apraxia, and nystagmus), renal cysts, and hepatic fibrosis. Respiratory abnormalities, as apnea and hyperpnea, may be present, as well as mental retardation. Since the clinical findings of JS are quite heterogeneous, determination of radiological findings is essential.

Molecular Characterization and Genetic Diversity Study in F3 Population of Rice

2013 ◽  
Vol 20 (1-2) ◽  
pp. 1-8
Author(s):  
MM Rahman ◽  
L Rahman ◽  
SN Begum ◽  
F Nur
Keyword(s):  
Genetic Distance ◽  
Gene Diversity ◽  
Random Amplified Polymorphic Dna ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Polymorphic Loci ◽  
Rice Genotypes ◽  
High Level ◽  
Genetic Diversity Study ◽  
Diversity Study

Random Amplified Polymorphic DNA (RAPD) assay was initiated for molecular genetic analysis among 13 F3 rice lines and their parents. Four out of 15 decamer random primers were used to amplify genomic DNA and the primers yielded a total of 41 RAPD markers of which 37 were considered as polymorphic with a mean of 9.25 bands per primer. The percentage of polymorphic loci was 90.24. The highest percentage of polymorphic loci (14.63) and gene diversity (0.0714) was observed in 05-6 F3 line and the lowest polymorphic loci (0.00) and gene diversity (0.00) was found in 05-12 and 05-15 F3 lines. So, relatively high level of genetic variation was found in 05-6 F3 line and it was genetically more diverse compared to others. The average co-efficient of gene differentiation (GST) and gene flow (Nm) values across all the loci were 0.8689 and 0.0755, respectively. The UPGMA dendrogram based on the Nei’s genetic distance differentiated the rice genotypes into two main clusters: PNR-519, 05-19, 05-14, 05-12 and 05-17 grouped in cluster 1. On the other hand, Baradhan, 05-9, 05-13, 05-11, 05-5, 05-6, 05-1, 05-4, 05-15 and 05-25 were grouped in cluster 2. The highest genetic distance (0.586) was found between 05-4 and 05-17 F3 lines and they remain in different cluster.DOI: http://dx.doi.org/10.3329/pa.v20i1-2.16839 Progress. Agric. 20(1 & 2): 1 – 8, 2009

Diagnosis and Management of Cardiomyopathies – A Focus on Genetics, Cardiac Magnetic Resonance and Clinical Features

2011 ◽  
Vol 7 (3) ◽  
pp. 225
Author(s):  
Gianfranco Sinagra ◽  
Michele Moretti ◽  
Giancarlo Vitrella ◽  
Marco Merlo ◽  
Rossana Bussani ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Imaging Techniques ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Routine Clinical Practice ◽  
Clinical Approach ◽  
Diagnosis And Management ◽  
Made In

In recent years, outstanding progress has been made in the diagnosis and treatment of cardiomyopathies. Genetics is emerging as a primary point in the diagnosis and management of these diseases. However, molecular genetic analyses are not yet included in routine clinical practice, mainly because of their elevated costs and execution time. A patient-based and patient-oriented clinical approach, coupled with new imaging techniques such as cardiac magnetic resonance, can be of great help in selecting patients for molecular genetic analysis and is crucial for a better characterisation of these diseases. This article will specifically address clinical, magnetic resonance and genetic aspects of the diagnosis and management of cardiomyopathies.

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