Publications by authors named "Godelieve Morel"
Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants.
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- Fetal Alcohol Spectrum Disorders (FASDs) are often underdiagnosed or misdiagnosed, highlighting the need for quicker identification and better support for affected families.* -
- A study involving 147 children and adolescents with FASDs revealed that 42.9% had paternal alcohol consumption and 33.3% were born prematurely, with many exhibiting learning difficulties and motor skill disabilities.* -
- The study found that almost 23% of these patients also showed genetic anomalies, suggesting that FASDs entail a combination of prenatal alcohol exposure, prematurity, challenging social conditions, and genetic factors.*
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- Prenatal exome sequencing (pES) is increasingly used to diagnose fetuses with structural defects, identifying additional conditions in about 30% who have normal chromosomal microarray analysis (CMA).
- A study categorized prenatal phenotypes for fetuses with pathogenic variants, finding typical features in 67.9% of cases, while uncommon or unreported features complicated some interpretations.
- Recommendations include standardizing prenatal feature descriptions, enhancing follow-up practices, and collecting larger datasets to improve pES analysis.
Article Synopsis
- * A study examined 28 patients from 18 families with loss of function (LOF) variants, revealing a spectrum of neurological and developmental issues including global developmental delay, intellectual disabilities, microcephaly, and behavioral abnormalities.
- * Research using fruit flies showed that mutations in the RBF gene mirrored symptoms seen in patients, affecting brain morphology and movement, and highlighted the importance of ongoing RBL2 expression in mature neurons for normal locomotion, suggesting potential therapeutic avenues.
Larsen of La Réunion Island syndrome (LRS) is an autosomal recessive condition associated with multiple large joint dislocations, clubfeet, severe dwarfism, and distinctive facial features. LRS is caused by a recurrent homozygous variant in B4GALT7 gene with a founder effect in La Réunion population. Proteoglycans (PG) that are a major component of the extracellular matrix, are composed of a core protein connected to a glycosaminoglycans side chain via a tetrasaccharide linker region.
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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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- Cochleovestibular dysfunctions are uncommon and often misdiagnosed, with a specific genetic mutation linked to these conditions.
- A pathogenic variant in the RIPOR2 gene was found in Tunisian siblings who have severe hearing and balance issues.
- Unlike the patients, animal models with Ripor2 mutations (like mice and zebrafish) maintain normal vestibular function, highlighting differences in how this mutation affects different species.
Background: Fetal Alcohol Spectrum Disorders (FASD) are the most common cause of neurocognitive impairment and social inadaptation, affecting 1 birth in 100. Despite the existence of precise diagnostic criteria, the diagnosis remains difficult, often confounded with other genetic syndromes or neurodevelopmental disorders. Since 2016, Reunion Island has been a pilot region for the identification, diagnosis, and care of FASD in France.
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- A pilot study in France used trio-ES on 150 fetuses with significant ultrasound anomalies, with a focus on influencing pregnancy management, and found a causal diagnosis in 34% of cases within about 28 days.
- The study demonstrated a high diagnostic yield for trio-ES, comparable to postnatal diagnosis, indicating its potential for routine use in prenatal care when anomalies are detected.
Microphthalmia, Anophthalmia and Coloboma (MAC) form a spectrum of congenital eye malformations responsible for severe visual impairment. Despite the exploration of hundreds of genes by High-Throughput Sequencing (HTS), most of the patients remain without genetic diagnosis. One explanation could be the not yet demonstrated involvement of somatic mosaicism (undetected by conventional analysis pipelines) in those patients.
View Article and Find Full Text PDFThe Bailey-Bloch congenital myopathy, also known as Native American myopathy (NAM), is an autosomal recessive congenital myopathy first reported in the Lumbee tribe people settled in North Carolina (USA), and characterized by congenital weakness and arthrogryposis, cleft palate, ptosis, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH) triggered by anesthesia. NAM is linked to STAC3 gene coding for a component of excitation-contraction coupling in skeletal muscles. A homozygous missense variant (c.
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- Peters' anomaly (PA) is a rare eye condition marked by issues like corneal opacity and adhesions related to the eye's anterior segment, linked to several genes such as B3GLCT and PAX6.
- Researchers studied 95 PA patients using advanced genetic techniques and found genetic defects in about one-third of them, with B3GLCT and PAX6 being the most common culprits.
- Notably, they discovered SOX2, a gene associated with microphthalmia, in some PA patients, highlighting its unexpected role in this condition and the need for further genetic exploration in PA cases.
Loss-of-function variants in KMT2D are responsible for Kabuki syndrome type 1 (KS1). In the last 5 years, missense variants in exon 38 or 39 in KMT2D have been found in patients exhibiting a new phenotype with multiple malformations and absence of intellectual disability, distinct from KS1. To date, only 16 cases have been reported with classic features of hearing loss, abnormality of the ear, lacrimal duct defects, branchial sinus/neck pits, choanal atresia (CA), athelia, hypo(para)thyroidism, growth delay, and dental anomalies.
View Article and Find Full Text PDFCockayne syndrome (CS) is a multisystem degenerative disorder divided in 3 overlapping subtypes, with a continuous phenotypic spectrum: CS2 being the most severe form, CS1 the classical form and CS3 the late-onset form. Failure to thrive and growth difficulties are among the most consistent features of CS, leaving affected individuals vulnerable to numerous medical complications, including adverse effects of undernutrition, abrupt overhydration and overfeeding. There is thus a significant need for specific growth charts.
View Article and Find Full Text PDFPITX1 is a homeobox transcription factor essential for hindlimb morphogenesis. Two PITX1-related human disorders have been reported to date: PITX1 ectopic expression causes Liebenberg syndrome, characterized by malformation of upper limbs showing a "lower limb" appearance; PITX1 deletions or missense variation cause a syndromic picture including clubfoot, tibial hemimelia, and preaxial polydactyly. We report two novel PITX1 missense variants, altering PITX1 transactivation ability, in three individuals from two unrelated families showing a distinct recognizable autosomal dominant syndrome, including first branchial arch, pelvic, patellar, and male genital abnormalities.
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- - Whole mitochondrial DNA sequencing is now routinely used in clinical labs to identify mitochondrial disease in patients, aided by Next Generation Sequencing, which has revealed many new mtDNA variants.
- - Alongside an increase in identified pathogenic variants, there has also been a rise in variants of unknown significance (VUS), complicating their interpretation for patient treatment and counseling.
- - The study characterized eight heteroplasmic mtDNA variants, classifying some as "definitely pathogenic," while others remain "possibly pathogenic," showcasing the importance of single fiber studies in diagnosing low-level heteroplasmy cases.
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- - Segmental progeroid syndromes are rare genetic disorders that speed up certain aging features and have been researched since the 20th century.
- - The Molecular Genetics Laboratory in Marseille has been using NGS sequencing for four years to diagnose these syndromes in 66 patients, achieving a diagnostic success rate over 60% when there's a specific clinical suspicion.
- - The study identified significant genetic variants in many patients, proposed prenatal testing for some families, and emphasized that this method is an effective first step towards diagnosing these disorders before considering whole genome sequencing.
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- Kabuki syndrome (KS) is a rare genetic disorder marked by distinctive facial features, intellectual disability, and various physical malformations.
- In a study involving 177 individuals with KS, significant percentages displayed immunopathological issues: 44.1% had infection susceptibility, 58.2% had low immunoglobulin levels, and there were notable occurrences of autoimmune diseases.
- The findings underscore the critical need for regular screening and preventive care for these potentially serious health issues in KS patients.
An 11-year-old boy with psychomotor delay, exercise intolerance, ptosis and growth delay had a muscle biopsy showing typical mitochondrial alterations (60% of ragged-red fibers and 90% of cytochrome-c oxidase-deficient fibers). Next-generation sequencing revealed a novel heteroplasmic mutation (m.15958A>T) in the MTTP gene that encodes tRNA.
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