Zusammenfassung
Die Ursache neurokognitiver Entwicklungsstörungen mit Intelligenzminderung stellt eine der häufigsten Fragestellungen in der genetischen Sprechstunde dar. Obwohl mehr als 400 krankheitsverursachende Einzelgendefekte bekannt sind, machen Chromosomenaberrationen derzeit den größten Anteil der bekannten Ursachen aus. Mittels hochauflösender Array-Techniken lassen sich nach Ausschluss des Down-Syndroms bei unselektionierten Patienten in 18% der Fälle relevante chromosomale Imbalancen nachweisen, wobei die Aberrationen nur in 4% der Fälle auch primär mikroskopisch sichtbar wären. Mit zunehmender Auflösung steigt jedoch auch die Rate an detektierten Kopienzahl-Normvarianten, welche die Beurteilung der Befunde erschweren können. Indikatoren für krankheitsrelevante Aberrationen sind Aberrationsgröße, Gengehalt und Segregation innerhalb der Familie. Eine Kausalität kann letztlich aber nur dann belegt werden, wenn Vergleichsfälle mit ähnlichem Genotyp und Phänotyp vorliegen.
Abstract
Establishing an etiological diagnosis in patients with developmental neurocognitive disorders involving intellectual disability represents a common challenge in clinical genetics. Although more than 400 monogenic diseases with intellectual disability as a trait have been delineated, chromosomal disorders represent the majority of known causes to date. Excluding Down syndrome, high-resolution molecular karyotyping is able to reveal a causative chromosomal imbalance in 18% of unselected patients, while microscopic karyotyping would detect a causal aberration in only 4% of cases. Increasing resolution, however, also increases the number of benign copy number variants detected, which may hamper the interpretation of results. Indicators of disease associated copy number changes include aberration size, gene content and segregation of the aberration with the phenotype within a family. Ultimately, causality can only be proven when multiple cases with a similar genotype and phenotype have been observed.
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Der korrespondierende Autor weist auf folgende Beziehung(en) hin: Drittmittel von Novartis für FiaX-Therapiestudie.
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Oneda, B., Rauch, A. Molekulare Karyotypisierung in der Diagnostik neurokognitiver Entwicklungsstörungen. medgen 24, 94–98 (2012). https://doi.org/10.1007/s11825-012-0327-y
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DOI: https://doi.org/10.1007/s11825-012-0327-y
Schlüsselwörter
- „Comparative genomic hybridization“
- Chromosomenaberrationen
- Geistige Behinderung
- Neurokognitive Entwicklungsstörungen
- Einzelnukleotidpolymorphismen