Publications by authors named "Kitzis A"
Background: The majority of variants of unknown clinical significance (VUCS) in the CFTR gene are missense variants. While change on the CFTR protein structure or function is often suspected, impact on splicing may be neglected. Such undetected splicing default of variants may complicate the interpretation of genetic analyses and the use of an appropriate pharmacotherapy.
View Article and Find Full Text PDFThree Complex alleles associated with N1303K mutation and their molecular consequences.
Cell Mol Biol (Noisy-le-grand)
April 2022
Article Synopsis
- * This study aimed to identify complex alleles with the N1303K mutation among patients from Lebanon, Egypt, and France by using PCR amplification and DNA sequencing.
- * Results indicate that N1303K, along with associated polymorphisms, leads to abnormal CFTR mRNA splicing, affecting the protein's quality and quantity, which may influence the severity of Cystic Fibrosis symptoms.
Article Synopsis
- CHARGE syndrome is a rare genetic disorder linked to mutations in the CHD7 gene, leading to various congenital abnormalities.
- The study aimed to create a biological test for CHD7 protein to understand how specific genetic variants affect its function.
- Results showed that while the wild-type CHD7 effectively downregulated certain genes, the variants did not have the same effect, indicating they are nonfunctional and contribute to the disease.
Article Synopsis
- - CHARGE syndrome is a rare genetic disorder primarily caused by mutations in the CHD7 gene, often occurring as de novo mutations.
- - The study identifies a specific area with recurrent mutations in the CHD7 gene, highlighting a particular genomic context that makes these mutations impactful, including issues with natural acceptor sites.
- - By using computational analysis and experimental methods, the research shows that these mutations create new splice sites, suggesting that combining different diagnostic techniques could improve molecular diagnosis in patients.
Complexity of phenotypes induced by p.Asn1303Lys-CFTR correlates with difficulty to rescue and activate this protein.
Cell Mol Biol (Noisy-le-grand)
November 2017
Article Synopsis
- * The specific mutation c.3909C>G (p.Asn1303Lys) was analyzed for its impact on protein processing using immunofluorescence and western blot techniques.
- * Results indicated that the p.Asn1303Lys mutation leads to abnormal protein folding and function, suggesting that a combination of drugs may be necessary for effective treatment.
Article Synopsis
- - Cystic fibrosis is linked to mutations in the CFTR gene, which can impact the CFTR protein's location and function as a chloride channel in epithelial cells.
- - The study focused on the c.965T>C mutation, which causes a change from valine to alanine in the CFTR protein, using both computer simulations and cell analysis.
- - Results indicated that this specific mutation likely does not affect the CFTR protein's function in the tested cell line, but doctors should exercise caution and monitor patients with this mutation if they have other mutations as well.
Article Synopsis
- The CFTR gene has over 2,000 variants, most of which are rare, hindering genetic counseling and patient care due to limited data.
- CFTR-France has created a specialized database containing 16,819 variant records from individuals with cystic fibrosis and related disorders, aiding in the interpretation of these rare variants.
- This database combines clinical and genetic information to enhance understanding and classification of variants, serving as a vital resource for diagnostic labs and genetic counseling.
Cystic fibrosis (CF) occurrence in Arab populations is not common and still remains underidentified. Furthermore, the lack of disease awareness and diagnosis facilities have mislead the identification of cystic fibrosis for decades. The knowledge about cystic fibrosis (CF) in Egypt is very limited, and a few reports have drawn attention to the existence of CF or CFTR-related disorders (CFTR-RDs) in the Egyptian population.
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- Array comparative genomic hybridization (aCGH) is commonly used for diagnosing developmental delays and intellectual disabilities, but classic karyotyping is still important for cases with mosaicism.
- A 30-year-old patient with syndromic intellectual disability was identified to have a 22q13.2 microdeletion and mosaic trisomy 22, presenting various physical and developmental challenges.
- The study emphasizes the importance of using both aCGH and traditional karyotyping in genetic analyses to ensure accurate diagnoses, particularly in complex cases like mosaic trisomy.
Article Synopsis
- The study investigates how brain-derived neurotrophic factor (BDNF) levels and a specific gene variant (Val66Met) influence episodic memory in older adults, specifically looking at the role of physical activity in this interaction.
- Researchers divided 205 participants aged 55 and older into groups based on their physical activity levels and BDNF genetic profiles, finding that physical activity significantly impacted memory performance based on the genetic variant present.
- The results reveal that only those with the Val/Val variant showed improved episodic memory through physical activity, underscoring the importance of genetic factors in the relationship between exercise and cognitive health in the elderly.
Article Synopsis
- Hereditary Hemorrhagic Telangiectasia (HHT) syndrome, also known as Rendu-Osler-Weber syndrome, is a genetic vascular disorder caused by mutations in the ACVRL1 or ENG genes.
- The study focused on 23 nucleotide variations in the ACVRL1 gene found in over 400 patients, identifying 14 novel missense mutations and analyzing their functional impact, with 18 of 22 being found defective.
- Two specific mutations not only disrupted splicing but also likely led to mRNA degradation, supporting the haploinsufficiency model for HHT2 and illustrating the importance of combining functional and splicing analyses as diagnostic tools for clinicians.
Article Synopsis
- Cystic Fibrosis, a common recessive genetic disorder in Caucasians, is linked to mutations in the CFTR gene, with c.3909C>G being one of the most prevalent mutations, especially in the Lebanese population.
- Researchers conducted a comprehensive screening of the CFTR gene in Lebanese patients, identifying the complex allele c.[744-33GATT(6); 869+11C>T], which frequently occurs alongside the c.3909C>G mutation.
- Cell studies using hybrid minigene constructs showed that while c.3909C>G does not affect splicing, the associated complex allele causes minor skipping of exons during the splicing process.
Article Synopsis
- Recent findings have led to a focus on a specific 78 kb region near the SOX9 gene, which is critical for testis development, revealing duplications related to 46,XX and 46,XY DSD cases.
- In a study of three patients with 46,XX testicular DSD and azoospermia, two brothers were found to have a duplication of about 83.8 kb upstream of SOX9, refining the potential genetic links to 46,XX-SRY negative DSD and suggesting key
Article Synopsis
- CFTR (cystic fibrosis transmembrane conductance regulator) is a chloride channel found in epithelial cells, and its defective version leads to reduced stability at the cell membrane due to improper trafficking.
- The study focuses on the role of Cdc42, a small GTPase, in the turnover and trafficking of CFTR, revealing that inhibiting Cdc42 disrupts CFTR activity and increases its endocytosis, implying that Cdc42 is important for anchoring CFTR to the cytoskeleton.
- The research concludes that Cdc42 is critical for various aspects of CFTR lifecycle, including its biosynthesis, stability at the membrane, and regulation of endocytosis, thereby influencing CFTR degradation processes.
Article Synopsis
- The study investigates the effects of the c.1392G>T CFTR mutation found in a cystic fibrosis (CF) patient, focusing on how this mutation alters gene splicing and protein functionality.
- Various experiments, including minigene studies and analyses of nasal cell mRNA, reveal that the mutation leads to complete deletion of exon 10 and a frameshift transcript, worsening the impact of a nearby TG(11)T(5) polymorphism.
- Findings show that the resulting p.Lys464Asn protein lacks maturation and proper localization, leading to absent CFTR activity and demonstrating the need for thorough analysis of complex CFTR mutations for accurate classification and treatment strategies.
Background: Intramedullary ependymomas are rare and benign tumors in the adult. Little is known about their physiopathology, but the implication of the NF2 gene is suspected because of their presence in a third of patients with type 2 neurofibromatosis (NF2), a disorder caused by mutation of the NF2 gene.
Methods: We conducted a clinical and genetic study of a family in which 5 of 9 members suffered from intramedullary ependymoma.
Article Synopsis
- A 22-year-old woman was diagnosed with osteogenesis imperfecta (OI), tricho-dento-osseous (TDO) syndrome, and intellectual disability, prompting genetic analysis.
- Whole genome analysis showed a 3 Mb increase in chromosome 7 and a 3.4 Mb deletion in chromosome 17, with FISH analysis revealing a complex chromosomal rearrangement involving these areas.
- Family studies indicated that the woman's mother and uncle had similar genetic anomalies, and the deleted region contains key genes like COL1A1 and DLX3, which are linked to her conditions, while CACNA1G may explain her intellectual disability.
Article Synopsis
- The study investigated the phenotypic expressivity related to NRXN1 gene deletions, analyzing the largest patient cohort to date, alongside existing literature.
- Researchers found common features in 25 new cases of NRXN1 deletions, including high rates of intellectual disability, language delay, autism, seizures, and hypotonia, aligning with known phenotypes.
- The study concluded that NRXN1 exonic deletions contribute to neurodevelopmental disorders and suggested that additional rare copy number variants might influence phenotype severity.
Article Synopsis
- CFTR exon 10 has duplicate sequences in the human genome that can complicate mutation detection due to their polymorphic nature, which means variations can appear similar to genuine mutations.
- Previous work developed a PCR methodology specifically to isolate exon 10 and avoid these ectopic regions, improving mutation analysis accuracy.
- This study confirmed that certain previously described mutations (c.1392G>T, c.1338_1339delAT, c.1235delC, and c.1247A>G) are legitimate CFTR exon 10 mutations and not just variations from duplicate sequences, validating the new analysis technique.
Article Synopsis
- CHARGE syndrome is a rare congenital disorder primarily linked to CHD7 gene mutations, with this study examining 40 cases of the condition in fetuses, expanding from a previous report of 10.
- The study revealed that fetuses showed a higher male ratio, suggesting greater severity in males, and identified common characteristics such as ear anomalies and brain malformations, while intrauterine growth retardation was not observed.
- The findings help refine the clinical understanding of CHARGE syndrome in fetuses, aiding in the diagnosis of the condition after severe malformation detections during pregnancy.
Article Synopsis
- Genotype-phenotype correlations in cystic fibrosis (CF) face challenges due to variability linked to CFTR gene mutations and complex alleles, prompting a study to clarify the significance of specific complex alleles.
- A total of 153 patients with certain mutations were analyzed, revealing that only three had classical CF, while others presented variations like isolated infertility or were healthy despite severe mutations.
- Functional studies indicated that specific mutations, particularly p.Gly149Arg, lead to severe processing defects, while others moderately or mildly affect CFTR function, underscoring the need for thorough investigations to understand mutation impacts on CF clinical symptoms.
Article Synopsis
- CHARGE syndrome is a genetic disorder characterized by a combination of ocular coloboma, heart malformations, choanal atresia, growth or central nervous system issues, genital anomalies, and ear anomalies.
- Prenatal diagnosis of CHARGE syndrome can be indicated through the detection of certain major anomalies during ultrasound exams.
- In this case, researchers confirmed the diagnosis by identifying a mutation in the CHD7 gene in a family with no previous history of the syndrome.
Article Synopsis
- The study investigates how common cystic fibrosis (CF) is in fetuses that show a specific ultrasound sign called nonvisualized fetal gallbladder (NVFGB) when referred for genetic testing.
- Researchers analyzed genetic testing results from 2002 to 2009 for fetuses with NVFGB and correlated their findings with a related ultrasound sign known as fetal echogenic bowel (FEB).
- Results showed that the likelihood of CF was significantly higher in fetuses with both NVFGB and FEB compared to those with FEB alone, suggesting NVFGB is an important risk factor for CF.