Long-read genome sequencing resolves a complex 13q structural variant associated with syndromic anophthalmia.
Am J Med Genet A
; 188(5): 1589-1594, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35122461
ABSTRACT
Microphthalmia, anophthalmia, and coloboma (MAC) are a heterogeneous spectrum of anomalous eye development and degeneration with genetic and environmental etiologies. Structural and copy number variants of chromosome 13 have been implicated in MAC; however, the specific loci involved in disease pathogenesis have not been well-defined. Herein we report a newborn with syndromic degenerative anophthalmia and a complex de novo rearrangement of chromosome 13q. Long-read genome sequencing improved the resolution and clinical interpretation of a duplication-triplication/inversion-duplication (DUP-TRP/INV-DUP) and terminal deletion. Sequence features at the breakpoint junctions suggested microhomology-mediated break-induced replication (MMBIR) of the maternal chromosome as the origin. Comparing this rearrangement to previously reported copy number alterations in 13q, we refine a putative dosage-sensitive critical region for MAC that might provide new insights into its molecular etiology.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anoftalmia
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Coloboma
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Microftalmia
Tipo de estudo:
Diagnostic_studies
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Risk_factors_studies
Limite:
Humans
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Newborn
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article