Publications by authors named "Tania Attie-Bitach"

Pathogenic variants in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial function. Within this group, an increasing number of families have been identified, where Mendelian genetic disorders implicate defective mitochondrial RNA biology. The PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs.

View Article and Find Full Text PDF

Purpose: MYRF-related cardiac-urogenital syndrome (MYRF-CUGS) is a rare condition associated with heterozygous MYRF variants. The description of MYRF-CUGS phenotype is mostly based on postnatal cases and 36 affected individuals have been published so far. We aim now to delineate the prenatal phenotype of MYRF-CUGS by reporting clinical data from fetuses and neonates with a pathogenic MYRF variant.

View Article and Find Full Text PDF

Objective: Prenatal whole exome sequencing (pES) is increasingly prescribed for fetuses with ultrasound anomalies. Starting from the local French prenatal medicine practice, healthcare system and legal landscape, we aimed to address the broad medical and ethical issues raised by the use of pES for women and couples as well as for prenatal care providers.

Method: The French Federation of Human Genetics established a working group composed of clinicians and biologists from all over France to discuss pES challenges.

View Article and Find Full Text PDF
Article Synopsis
  • Glutathione synthetase deficiency is a rare genetic disorder caused by mutations in the GSS gene, leading to varying severity levels, from mild hemolytic anemia to severe neurological issues and even neonatal death.
  • A study on two fetal siblings revealed multiple congenital anomalies, such as limb malformations, cleft palate, and heart defects, linked to specific genetic variants in the GSS gene.
  • Genome sequencing and analysis indicated that these genetic variants likely caused disruptions in protein expression and metabolic processes, suggesting a broader range of phenotypic effects associated with glutathione synthetase deficiency.
View Article and Find Full Text PDF

Objective: Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult-onset limb-girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging.

Methods: In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023.

View Article and Find Full Text PDF
Article Synopsis
  • Fontaine progeroid syndrome (FPS) is a newly identified genetic disorder linked to mutations in the SLC25A24 gene, resulting in severe physical abnormalities such as craniosynostosis and growth restrictions.
  • The first documented prenatal cases during the second trimester show different phenotypic features, including encephalocele and nephromegaly, while lacking some typical signs of FPS seen after birth.
  • The study highlights the importance of genetic testing methods like exome/genome sequencing for diagnosing rare syndromes, suggesting that FPS may involve a novel inheritance pattern.
View Article and Find Full Text PDF
Article Synopsis
  • - TOKAS (Tonne-Kalscheuer syndrome) is a rare genetic disorder linked to multiple congenital anomalies, predominantly affecting males, and only 7 prenatal cases were previously documented among 41 patients.
  • - A study identified 11 new cases from 6 French families through collaboration, revealing common features like diaphragmatic hernia, sex development differences, and various malformations, along with previously unreported conditions.
  • - This research marks the first comprehensive fetal cohort for TOKAS, enhancing understanding of its clinical traits and genetic variants, with a significant recurrence of a specific genetic mutation noted in many cases.
View Article and Find Full Text PDF
Article Synopsis
  • There are about 8,000 rare diseases that affect around 400 million people, with many not getting diagnosed quickly.
  • Ciliopathies, a type of rare disease, are hard to diagnose because they have many different symptoms and genetic causes.
  • The study tested three online systems that help diagnose these diseases using patient records, but they didn't perform as well as expected and highlighted the need for better tools and data quality.
View Article and Find Full Text PDF

Carpenter syndrome (CRPTS) is a rare autosomal recessive condition caused by biallelic variants in genes that encode negative regulators of hedgehog signalling (RAB23 [CRPT1] or, more rarely, MEGF8 [CRPT2]), and is characterised by craniosynostosis, polysyndactyly, and other congenital abnormalities. We describe a further six families comprising eight individuals with MEGF8-associated CRPT2, increasing the total number of reported cases to fifteen, and refine the phenotype of CRPT2 compared to CRPT1. The core features of craniosynostosis, polysyndactyly and (in males) cryptorchidism are almost universal in both CRPT1 and CRPT2.

View Article and Find Full Text PDF
Article Synopsis
  • The study aimed to develop an automatic tool that can identify specific ear characteristics in fetuses affected by CHARGE and MFDGA syndromes compared to controls.
  • Researchers trained the model using ear photographs of children with these syndromes and applied machine learning techniques to classify images of fetuses.
  • Results showed that the model could accurately classify the fetuses with an overall accuracy of 72.6%, indicating promising potential, but further validation is needed before it can be used clinically.
View Article and Find Full Text PDF

The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remain unknown. Here we developed a semi-automated live/fixed correlative imaging method to map basal radial glial cell division modes in early fetal tissue and cerebral organoids.

View Article and Find Full Text PDF

Severe ventriculomegaly is a rare congenital brain defect, usually detected in utero, of poor neurodevelopmental prognosis. This ventricular enlargement can be the consequence of different mechanisms: either by a disruption of the cerebrospinal fluid circulation or abnormalities of its production/absorption. The aqueduct stenosis is one of the most frequent causes of obstructive ventriculomegaly, however, fewer than 10 genes have been linked to this condition and molecular bases remain often unknown.

View Article and Find Full Text PDF
Article Synopsis
  • The study aims to create a new AI-based model for identifying Kabuki Syndrome (KS) from 2D facial photos, differentiating between its two types: KS1 (KMT2D-related) and KS2 (KDM6A-related).
  • Utilizing over 1,400 facial images from 634 patients and controls, researchers incorporated machine learning techniques, specifically XGboost, for improved predictive accuracy.
  • The proposed model achieved an impressive accuracy of 95.8% in identifying KS and showed better performance than existing AI solutions and expert evaluations.
View Article and Find Full Text PDF

Purpose: Oral-facial-digital (OFD) syndromes are genetically heterogeneous developmental disorders, caused by pathogenic variants in genes involved in primary cilia formation and function. We identified a previously undescribed type of OFD with brain anomalies, ranging from alobar holoprosencephaly to pituitary anomalies, in 6 unrelated families.

Methods: Exome sequencing of affected probands was supplemented with alternative splicing analysis in patient and control lymphoblastoid and fibroblast cell lines, and primary cilia structure analysis in patient fibroblasts.

View Article and Find Full Text PDF

Neu Laxova syndrome (NLS) is a rare and lethal congenital disorder characterized by severe intra-uterine growth retardation (IUGR), ichthyosis, abnormal facial features, limb abnormalities with arthrogryposis and a wide spectrum of severe malformations of the central nervous system (CNS). NLS is due to biallelic variants in three genes previously involved in serine-deficiency disorders (PHGDH, PSAT1 and PSPH), extending the phenotypic spectrum of these disorders.

View Article and Find Full Text PDF

Primrose syndrome is a very rare congenital malformation. Symptoms of this disorder may appear during childhood, but the diagnosis is identified in adulthood in the majority of cases. The prenatal diagnosis of Primrose syndrome is not developed in the literature.

View Article and Find Full Text PDF

Purpose: BCL11B-related disorder (BCL11B-RD) arises from rare genetic variants within the BCL11B gene, resulting in a distinctive clinical spectrum encompassing syndromic neurodevelopmental disorder, with or without intellectual disability, associated with facial features and impaired immune function. This study presents an in-depth clinico-biological analysis of 20 newly reported individuals with BCL11B-RD, coupled with a characterization of genome-wide DNA methylation patterns of this genetic condition.

Methods: Through an international collaboration, clinical and molecular data from 20 individuals were systematically gathered, and a comparative analysis was conducted between this series and existing literature.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates anomalies of the corpus callosum (ACC), a common brain malformation, highlighting that the genetic causes of ACC without intellectual disability (ID) are not well understood.
  • Researchers identified a new dominant gene associated with ACC, reporting on nine individuals with a specific genetic variant linked to both familial inheritance and normal cognitive function.
  • Findings indicate that this gene may lead to ACC while maintaining normal intellectual abilities, suggesting a broader range of physical malformations associated with it beyond just eye conditions.
View Article and Find Full Text PDF

Introduction: Mandibulo-Facial Dysostosis with Microcephaly (MFDM) is a rare disease with a broad spectrum of symptoms, characterized by zygomatic and mandibular hypoplasia, microcephaly, and ear abnormalities. Here, we aimed at describing the external ear phenotype of MFDM patients, and train an Artificial Intelligence (AI)-based model to differentiate MFDM ears from non-syndromic control ears (binary classification), and from ears of the main differential diagnoses of this condition (multi-class classification): Treacher Collins (TC), Nager (NAFD) and CHARGE syndromes.

Methods: The training set contained 1,592 ear photographs, corresponding to 550 patients.

View Article and Find Full Text PDF

Phosphoinositides (PIs) are membrane phospholipids produced through the local activity of PI kinases and phosphatases that selectively add or remove phosphate groups from the inositol head group. PIs control membrane composition and play key roles in many cellular processes including actin dynamics, endosomal trafficking, autophagy, and nuclear functions. Mutations in phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] phosphatases cause a broad spectrum of neurodevelopmental disorders such as Lowe and Joubert syndromes and congenital muscular dystrophy with cataracts and intellectual disability, which are thus associated with increased levels of PI(4,5)P2.

View Article and Find Full Text PDF
Article Synopsis
  • CREBBP mutations can cause multiple syndromes, including Rubinstein-Taybi syndrome and a newer condition called Menke-Hennekam syndrome, linked to specific missense mutations.
  • A case study involved a fetus with observable abnormalities, where whole exome sequencing identified a CREBBP mutation known to lead to Menke-Hennekam syndrome.
  • Prenatal diagnosis of this rare syndrome relies on molecular methods like WES since the symptoms are often vague and varied, highlighting the need for genetic testing when unusual signs are detected during pregnancy.
View Article and Find Full Text PDF
Article Synopsis
  • * Most variants of the SMARCC1 gene are loss of function (LoF) and typically passed down from unaffected parents, suggesting incomplete penetrance.
  • * This research presents the first antenatal cases of SMARCC1 LoF variants found through Whole Genome Sequencing, highlighting the challenges in diagnosis and genetic counseling due to its inheritance patterns.
View Article and Find Full Text PDF

CHARGE syndrome, due to CHD7 pathogenic variations, is an autosomal dominant disorder characterized by a large spectrum of severity. Despite the great number of variations reported, no clear genotype-to-phenotype correlation has been reported. Unsupervised machine learning and clustering was undertaken using a retrospective cohort of 42 patients, after deep radiologic and clinical phenotyping, to establish genotype-phenotype correlation for CHD7-related CHARGE syndrome.

View Article and Find Full Text PDF
Article Synopsis
  • Dominant variants in the RARB gene cause MCOPS12, a type of microphthalmia that comes with various birth defects and developmental delays, impacting 25 individuals in this study.
  • The research employed transcriptional assays and structural analysis to evaluate how these RARB variants affect its typical function, revealing both gain-of-function and loss-of-function activities.
  • Findings indicate that while RARB disruption leads to a variety of clinical outcomes, some affected individuals may not show key symptoms like eye abnormalities or motor issues, highlighting the complexity of these genetic variations.
View Article and Find Full Text PDF