Publications by authors named "Marianne Till"
Article Synopsis
- Tatton-Brown-Rahman syndrome (TBRS) is a genetic disorder characterized by overgrowth, intellectual disability, and distinct facial features, resulting from mutations in a gene that regulates DNA methylation.* -
- A study of 24 French patients identified 17 new genetic variants, confirming that 100% showed intellectual disability, 96% had distinctive facial traits, and 87% exhibited overgrowth, alongside novel symptoms like hypertrichosis.* -
- The findings enhance the understanding of TBRS's clinical presentation, aiding in diagnosis and patient care by clarifying its genetic and phenotypic diversity.*
Article Synopsis
- Xq28 int22h-1/int22h-2 duplication results from recombination between specific genetic repeats and is linked to a form of intellectual disability along with recurrent infections and atopic diseases.
- In a study involving 15 families, many carriers exhibited mild or no symptoms, suggesting that the condition can manifest variably.
- The findings point towards potential incomplete penetrance, meaning not all carriers show obvious signs of the condition, indicating a need for further research to understand the genetic implications better.
Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases.
Am J Med Genet A
April 2024
Article Synopsis
- - Cat Eye Syndrome (CES) is a rare genetic disorder linked to a marker chromosome from chromosome 22, leading to diverse symptoms including iris coloboma, anal atresia, and preauricular tags, but these are present in less than half of the cases.
- - An international study of 43 CES patients found that only 16% displayed all three classic symptoms, while 9% showed none; additional issues such as cardiac anomalies (51%) and intellectual disabilities (47%) were also common.
- - The study highlights the significance of supernumerary marker chromosomes (sSMC), found in 91% of cases, with many parents showing mild traits, emphasizing the need for genetic counseling regarding recurrence risks.
Article Synopsis
- This study focuses on the gene RAB11B, which has been linked to severe intellectual disability, aiming to validate its role in neurodevelopmental disorders.* -
- Researchers identified seven new individuals with genetic variants in RAB11B, analyzing their clinical features and using molecular modeling to understand the structural effects of these variants.* -
- Findings indicate a strong correlation between the specific genetic variants and the severity of symptoms, with certain mutations linked to more severe disabilities while others lead to milder issues like epilepsy.*
Article Synopsis
- Chromoanagenesis is a cellular process causing complex chromosomal rearrangements during a significant event, potentially leading to genetic material loss or gain and various traits, typically occurring sporadically but can also be inherited.
- In a study involving six families, researchers investigated how asymptomatic parents passed on these rearrangements to their children, using karyotyping, fluorescent in situ hybridization, chromosomal microarray, and whole genome sequencing to analyze the chromosomal changes.
- The findings suggest that chromoanagenesis can occur without affecting the parent's health or fertility, and prenatal testing using chromosomal microarray is recommended to identify any genetic imbalances in offspring from these families.
Article Synopsis
- * Researchers analyzed ultrasound data from 22 fetuses with the 6qter deletion, finding significant brain abnormalities such as cerebellar hypoplasia and ventricular enlargement, alongside other structural issues.
- * The results reveal common prenatal sonographic markers for the 6q deletion syndrome and underscore the need for chromosomal microarray analysis to detect related genetic deletions in cases with observed malformations.
Congenital combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare autosomal recessive disease resulting in hemorrhagic symptoms usually associated with developmental disorders and bone abnormalities. Pathogenic variants in two genes encoding enzymes of the vitamin K cycle, GGCX and VKORC1, can lead to this disorder. We present the case of a male fetus with a brachytelephalangic chondrodysplasia punctata (CDP), absence of nasal bone, growth restriction, and bilateral ventriculomegaly at 18 weeks of gestation.
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- * A study investigated 13 missense variants of PTCHD1, including both previously known and novel mutations found in male patients with intellectual disability (ID) and autism spectrum disorder (ASD).
- * Functional tests revealed that six of these variants disrupt PTCHD1 protein levels and cause retention in the endoplasmic reticulum, indicating they may be pathogenic and supporting PTCHD1's role in ID and ASD.
Article Synopsis
- - Mosaic Variegated Aneuploidy Syndrome (MVA) is a rare genetic disorder that leads to a mix of abnormal chromosome numbers in different tissues, resulting in symptoms like growth retardation, microcephaly, and learning disabilities.
- - Two adult brothers with MVA, born to related Moroccan parents, exhibited severe growth issues, facial differences, and skeletal and dental problems, along with specific chromosome alterations identified in their blood.
- - A genetic duplication in the CEP57 gene was found in both brothers, suggesting a possible mechanism behind this duplication called FoSTeS, and highlighting the importance of genetic testing for patients with such symptoms.
Article Synopsis
- The report details a case of a 19-year-old male with mosaic trisomy 13, characterized by various health issues including intellectual disability and heart defects.
- Genetic analysis revealed that the patient has some cells with an extra chromosome from a nonreciprocal translocation inherited from his healthy mother.
- This is only the second known instance of a patient with trisomy 13 mosaicism experiencing severe aortic root dilation, and the authors explore potential mechanisms behind the mosaic condition, particularly the instability of interstitial telomeres.
Article Synopsis
- Structural variants (SVs), like copy number variants (CNVs) and balanced chromosome rearrangements (ABCRs), are often difficult to detect using traditional short-read sequencing methods due to repetitive sequences, which makes long-read technologies like 10X Genomics' Chromium an interesting alternative.* -
- In a study involving 13 patients, short-read sequencing successfully identified known SVs in 10 of them, while the linked-read technology also detected 10 SVs, including one additional variant missed by the short-read method.* -
- Ultimately, the study concluded that the 10X Genomics linked-read strategy did not significantly enhance the detection or characterization of SVs compared to the short-read sequencing approach.*
Kabuki syndrome (KS, KS1: OMIM 147920 and KS2: OMIM 300867) is caused by pathogenic variations in KMT2D or KDM6A. KS is characterized by multiple congenital anomalies and neurodevelopmental disorders. Growth restriction is frequently reported.
View Article and Find Full Text PDFWe report the case of a girl with Asparagine synthetase deficiency, an autosomal recessive metabolic disorder characterized by severe microcephaly and epileptic encephalopathy secondary to pathogenic variants in the gene. Genetic explorations found a deletion of and a missense variant on the other allele detected respectively by array comparative genomic hybridization (CGH) and Sanger sequencing. Amino acid analysis provided a biochemical confirmation.
View Article and Find Full Text PDFPostnatal clinical phenotype of five patients with Pallister-Killian Syndrome (tetrasomy 12p): Interest of array CGH for diagnosis and review of the literature.
Mol Genet Genomic Med
October 2019
Article Synopsis
- Pallister-Killian syndrome (PKS) is a rare genetic disorder resulting from an extra chromosome 12p, leading to developmental delays, intellectual disabilities, and other congenital anomalies.
- In a study of five PKS patients, array Comparative Genomic Hybridization (aCGH) was used to identify genetic abnormalities, revealing tetrasomy 12p in four patients and confirming typical PKS features.
- The findings suggest that aCGH is an effective diagnostic tool for PKS using blood samples, recommending its use before more invasive methods like skin biopsies, as it can detect low levels of mosaicism.
Article Synopsis
- The study focused on 1p36 deletion syndrome, a genetic condition identified through prenatal testing, noted for developmental delays and facial features.
- Ten new cases were diagnosed around 19 weeks gestation, with deletion sizes varying from 1.6 to 16 Mb, most cases showing no other chromosomal abnormalities.
- Researchers suggest that certain ultrasound findings, like brain and heart defects, should alert doctors to the possibility of this syndrome.
Chromosomal microarray (CMA) is currently considered as a first-tier test in the genetic assessment of patients presenting with intellectual disability and/or multiple congenital abnormalities. The distinction between pathogenic CNVs, polymorphisms, and variants of unknown significance can be a diagnostic dilemma for cytogeneticists. The size of the CNV has been proposed as a useful criterion.
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- A study investigated balanced chromosomal rearrangements in patients with intellectual disabilities and congenital anomalies using next-generation sequencing to identify breakpoints at a molecular level.
- The research characterized breakpoints in 55 patients, revealing that 89% of chromosomal rearrangements were detected, with non-homologous end-joining identified as the primary repair mechanism.
- The study found that a diagnosis could be established in about 44.8% of patients, revealing disruptions in genes and suggesting that paired-end whole genome sequencing is effective for clinical applications in structural variation analysis.
Article Synopsis
- The study aimed to assess the effectiveness of chromosome microarray (CMA) testing in detecting genetic issues in fetuses diagnosed with isolated congenital heart defects (CHDs) after prenatal diagnosis.
- An analysis of 239 fetuses revealed 33 copy number variations (CNVs), with 19 being pathogenic, suggesting a 10.4% overall detection rate of anomalies, which varied by specific CHD type.
- The findings indicate that CMA offers a clinically significant increase in diagnostic yield (3.1%), emphasizing the need for testing beyond just the common 22q11.21 chromosomal abnormalities for isolated CHD cases.
Exome sequencing (ES) has revolutionized diagnostic procedures in medical genetics, particularly for developmental diseases. The variety and complexity of the information produced has raised issues regarding its use in a clinical setting. Of particular interest are patients' expectations regarding the information disclosed, the accompaniment provided, and the value patients place on these.
View Article and Find Full Text PDFThe original version of this Article contained an error in the spelling of the author Siddharth Banka, which was incorrectly given as Siddhart Banka. This has now been corrected in both the PDF and HTML versions of the Article.
View Article and Find Full Text PDFPurpose: Contiguous gene deletions are known to cause several neurodevelopmental syndromes, many of which are caused by recurrent events on chromosome 16. However, chromosomal microarray studies (CMA) still yield copy-number variants (CNVs) of unknown clinical significance. We sought to characterize eight individuals with overlapping 205-kb to 504-kb 16p13.
View Article and Find Full Text PDFChristianson syndrome (CS) is a X-linked neurodevelopmental disorder, including severe intellectual disability (ID), progressive microcephaly, ataxia, autistic behaviour (ASD), near absent speech, and epilepsy. Electrical status epilepticus in sleep (ESES) has been reported in two patients. We describe five male patients from three unrelated families with Christianson syndrome caused by a pathogenic nucleotide variation or a copy-number variation involving SLC9A6.
View Article and Find Full Text PDFChromosomal microarray (CMA) can detect pathogenic copy number variations in 15-20% of individuals with intellectual disability and in 10% of patients with autism spectrum disorders. The diagnostic rate in specific learning disorders (SLD) is unknown. Our study emphasizes the usefulness of CMA in the diagnostic workout assessment of familial SLD.
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