Publications by authors named "Elodie Lacaze"
While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder.
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- Variants of uncertain significance (VUS) present challenges in diagnosing rare diseases, and episignatures have emerged as potential biomarkers to help classify these variants.
- A study analyzed DNA methylation data from different groups, including carriers of pathogenic variants and healthy controls, using a k-nearest-neighbour classifier to assess the predictive abilities of various episignatures.
- Results revealed that while some signatures (ATRX, DNMT3A, KMT2D, NSD1) achieved 100% sensitivity, others (CREBBP-RSTS, CHD8) showed lower performance, indicating that not all episignatures are equally reliable for diagnostic use and highlighting the need for further validation with larger sample sizes.
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- - The study investigates the increasing frequency of multiple molecular diagnoses (MMDs) in individuals with congenital anomalies/intellectual disability (CA/ID) through clinical exome/genome sequencing, highlighting rates between 1.8% to 7.1% previously documented.
- - Out of 880 positive exome sequencing diagnoses analyzed from 2014 to 2021, MMDs were found in 3.5% of cases, with additional potential MMDs identified in 4.4% of individuals, indicating their significance in disease comprehension.
- - Emphasizing the necessity for reanalysis of sequencing data and collaboration among clinicians and biologists, the study underlines the importance of updated clinical information and enhanced bio
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- Exome sequencing has a high diagnostic yield (25%-70%) for rare diseases, revealing novel gene associations, but retrospective data reanalysis can be challenging for labs.
- The study employed a systematic reanalysis strategy utilizing daily PubMed searches and the GREP command-line tool to track new disease-gene associations over 18 months.
- From their queries, they identified 128 genes of interest and confirmed causal diagnoses in 21 individuals, showcasing that this efficient reanalysis method can enhance diagnostic outcomes in genetic research.
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- Variants in the PRSS1 and PRSS2 genes are linked to chronic pancreatitis (CP), prompting research into whether a deletion variant affecting two trypsinogen pseudogenes (PRSS3P2 and TRY7) might influence CP risk.
- A study analyzed this deletion in over 4,000 participants from different countries and found that it is associated with a protective effect against CP, especially in French, German, and Japanese populations.
- The research suggests that the deletion enhances the function of remaining genes, leading to regulated PRSS2 expression, which could be crucial in understanding CP susceptibility.
Assessment of age-dependent cancer risk for carriers of a predicted pathogenic variant (PPV) is often hampered by biases in data collection, with a frequent under-representation of cancer-free PPV carriers. TUMOSPEC was designed to estimate the cumulative risk of cancer for carriers of a PPV in a gene that is usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France.
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- Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is an iron-containing non-heme oxygenase linked to various neurological disorders in 34 individuals from 25 families with biallelic HPDL variants.
- These neurological disorders presented as conditions ranging from juvenile-onset spastic paraplegia to infantile-onset spasticity, often accompanied by severe developmental delays and respiratory issues.
- Experiments showed that HPDL is expressed in the nervous system, plays a role in motor function in zebrafish models, and its variants disrupt enzymatic function, suggesting a causative link between HPDL mutations and neurological diseases.
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- Biallelic pathogenic variants in the NTHL1 gene are linked to a hereditary cancer syndrome, increasing risks for adenomatous polyposis and colorectal cancer, as well as other tumors like breast and brain cancers.
- The study, using data from the French oncogenetic consortium, describes 10 patients with these variants, identifying them as the second-largest series on NTHL1, all of whom showed signs of adenomatous polyps.
- The findings suggest that testing for NTHL1 should be included in diagnostic panels for hereditary cancers, with recommendations for colon and extra-colonic cancer surveillance based on existing guidelines.
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- * A study of 18 individuals with mild intellectual disabilities and behavioral issues revealed that they are haploinsufficient for NFIB, with various genetic alterations including microdeletions and point mutations affecting the NFIB gene.
- * The analysis of a mouse model lacking NFIB in the cortex showed enlarged cerebral cortex while maintaining overall brain structure, suggesting that NFIB haploinsufficiency leads to intellectual disabilities accompanied by macrocephaly.
One of the main challenges in cancer genetics is responding to the exponential demand for genetic counseling, especially in patients with breast and/or ovarian cancer. To address this demand, we have set up a new procedure, based on pre-genetic counseling telephone interviews (PTI) followed by routing of patients: D1, a PTI is scheduled within 14 days; D7-D14, genetic counselors perform a 20 min PTI in order to establish a pre-genetic counseling file, by collecting personal and family medical history via a structured questionnaire and; D10-17, routing: pre-genetic counseling appointment files are analyzed by a cancer geneticist with 3 possible conclusions: (a) priority face-to-face genetic counseling (FTFGC) appointment with a cancer geneticist, if the genetic test results have an immediate therapeutic impact; (b) non-priority FTFGC with a genetic counselor, or (c) no FTFGC required or substitution by a more appropriate index case. In the context of breast and/or ovarian cancer, 1012 patients received PTIs, 39.
View Article and Find Full Text PDFBackground: Most microdeletions involving chromosome sub-bands 9q33.3-9q34.11 to this point have been detected by analyses focused on STXBP1, a gene known to cause early infantile epileptic encephalopathy 4 and other seizure phenotypes.
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- West syndrome is a type of epilepsy characterized by infantile spasms, hypsarrhythmia, and developmental delays, often caused by genetic mutations or deletions.
- The idiopathic form of West syndrome has a better prognosis and typically responds well to anti-epileptic treatments.
- A case study of a boy with idiopathic West syndrome revealed a de novo 15q13.3 microdeletion linked to epilepsy, suggesting that genetic exploration of this region should be considered in similar cases.
Nephroblastoma (Wilms' tumor; WT) is the most common renal tumor of childhood. To date, several genetic abnormalities predisposing to WT have been identified in rare overgrowth syndromes. Among them, abnormal methylation of the 11p15 region, GPC3 and DIS3L2 mutations, which are responsible for Beckwith-Wiedemann, Simpson-Golabi-Behmel and Perlman syndromes, respectively.
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