Current recommendations for the molecular evaluation of newly diagnosed holoprosencephaly patients

Autor: Véronique David, Daniel E. Pineda-Alvarez, Christèle Dubourg, Erich Roessler, Maximilian Muenke
Přispěvatelé: Cancer Genetics Branch, National Institute of Health (NIH)-National Human Genome Research Institute (NHGRI), Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Génétique Clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-hôpital Sud, This work was supported by the Division of Intramural Research of the National Human Genome Research Institute, the National Institutes of Health., Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, De Villemeur, Hervé
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Pathology
Time Factors
[SDV.GEN] Life Sciences [q-bio]/Genetics
MESH: Molecular Diagnostic Techniques
Bioinformatics
MESH: Smith-Lemli-Opitz Syndrome
disease genes
0302 clinical medicine
Holoprosencephaly
MESH: Eye Proteins
MESH: Nerve Tissue Proteins
[SDV.BDD]Life Sciences [q-bio]/Development Biology
Genetics (clinical)
0303 health sciences
Nuclear Proteins
MESH: Transcription Factors
Penetrance
MESH: Health Planning Guidelines
3. Good health
HPE
Molecular Diagnostic Techniques
MESH: Holoprosencephaly
Algorithms
musculoskeletal diseases
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
Health Planning Guidelines
Nerve Tissue Proteins
MESH: Algorithms
Newly diagnosed
Biology
ZIC2
Article
molecular diagnostics
03 medical and health sciences
Neuroimaging
[SDV.BDD] Life Sciences [q-bio]/Development Biology
MESH: Homeodomain Proteins
Genetics
medicine
Humans
MESH: Chromosome Aberrations
Hedgehog Proteins
multi-factorial inheritance
Craniofacial
Eye Proteins
030304 developmental biology
Chromosome Aberrations
Homeodomain Proteins
[SDV.GEN]Life Sciences [q-bio]/Genetics
MESH: Humans
MESH: Time Factors
MESH: Hedgehog Proteins
medicine.disease
Molecular diagnostics
Smith-Lemli-Opitz Syndrome
holoprosencephaly
Smith–Lemli–Opitz syndrome
MESH: Nuclear Proteins
030217 neurology & neurosurgery
Transcription Factors
Zdroj: American Journal of Medical Genetics Part C: Seminars in Medical Genetics
American Journal of Medical Genetics Part C: Seminars in Medical Genetics, Wiley, 2010, 154C (1), pp.93-101. ⟨10.1002/ajmg.c.30253⟩
American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2010, 154C (1), pp.93-101. ⟨10.1002/ajmg.c.30253⟩
ISSN: 1552-4868
1552-4876
DOI: 10.1002/ajmg.c.30253⟩
Popis: International audience; Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans and is typically characterized by different degrees of hemispheric separation that are often accompanied by similarly variable degrees of craniofacial and midline anomalies. HPE is a classic example of a complex genetic trait with "pseudo"-autosomal dominant transmission showing incomplete penetrance and variable expressivity. Clinical suspicion of HPE is typically based upon compatible craniofacial findings, the presence of developmental delay or seizures, or specific endocrinological abnormalities, and is then followed up by confirmation with brain imaging. Once a clinical diagnosis is made, a thorough genetic evaluation is necessary. This usually includes analysis of chromosomes by high-resolution karyotyping, clinical assessment to rule-out well recognized syndromes that are associated with HPE (e.g., Pallister-Hall syndrome, Smith-Lemli-Opitz syndrome and others), and molecular studies of the most common HPE associated genes (e.g., SHH, ZIC2 and SIX3). In this review, we provide current step-by-step recommendations that are medically indicated for the genetic evaluation of patients with newly diagnosed HPE. Moreover, we provide a brief review of several available methods used in molecular diagnostics of HPE and describe the advantages and limitations of both currently available and future tests as they relate to high throughput screening, cost, and the results that they may provide.
Databáze: OpenAIRE
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