Novel Alu insertion in the ZEB2 gene causing Mowat-Wilson syndrome.
Am J Med Genet A
; 194(8): e63581, 2024 08.
Article
en En
| MEDLINE
| ID: mdl-38600862
ABSTRACT
Alu elements are short, interspersed elements located throughout the genome, playing a role in human diversity, and occasionally causing genetic diseases. Here, we report a novel Alu insertion causing Mowat-Wilson syndrome, a rare neurodevelopmental disorder, in an 8-year-old boy displaying the typical clinical features for Mowat-Wilson syndrome. The variant was not initially detected in genome sequencing data, but through deep phenotyping, which pointed to only one plausible candidate gene, manual inspection of genome sequencing alignment data enabled us to identify a de novo heterozygous Alu insertion in exon 8 of the ZEB2 gene. Nanopore long-read sequencing confirmed the Alu insertion, leading to the formation of a premature stop codon and likely haploinsufficiency of ZEB2. This underscores the importance of deep phenotyping and mobile element insertion analysis in uncovering genetic causes of monogenic disorders as these elements might be overlooked in standard next-generation sequencing protocols.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Facies
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Elementos Alu
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Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc
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Enfermedad de Hirschsprung
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Discapacidad Intelectual
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Microcefalia
Límite:
Child
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Humans
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Male
Idioma:
En
Revista:
Am J Med Genet A
Asunto de la revista:
GENETICA MEDICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Dinamarca