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Next-generation phenotyping in Nigerian children with Cornelia de Lange syndrome.
Arlt, Annabelle; Knaus, Alexej; Hsieh, Tzung-Chien; Klinkhammer, Hannah; Bhasin, Meghna Ahuja; Hustinx, Alexander; Moosa, Shahida; Krawitz, Peter; Ekure, Ekanem.
Afiliación
  • Arlt A; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany.
  • Knaus A; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany.
  • Hsieh TC; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany.
  • Klinkhammer H; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany.
  • Bhasin MA; Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany.
  • Hustinx A; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany.
  • Moosa S; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany.
  • Krawitz P; Division of Molecular Biology and Human Genetics, Stellenbosch University and Medical Genetics, Tygerberg Hospital, Cape Town, South Africa.
  • Ekure E; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany.
Am J Med Genet A ; 194(9): e63641, 2024 09.
Article en En | MEDLINE | ID: mdl-38725242
ABSTRACT
Next-generation phenotyping (NGP) can be used to compute the similarity of dysmorphic patients to known syndromic diseases. So far, the technology has been evaluated in variant prioritization and classification, providing evidence for pathogenicity if the phenotype matched with other patients with a confirmed molecular diagnosis. In a Nigerian cohort of individuals with facial dysmorphism, we used the NGP tool GestaltMatcher to screen portraits prior to genetic testing and subjected individuals with high similarity scores to exome sequencing (ES). Here, we report on two individuals with global developmental delay, pulmonary artery stenosis, and genital and limb malformations for whom GestaltMatcher yielded Cornelia de Lange syndrome (CdLS) as the top hit. ES revealed a known pathogenic nonsense variant, NM_133433.4 c.598C>T; p.(Gln200*), as well as a novel frameshift variant c.7948dup; p.(Ile2650Asnfs*11) in NIPBL. Our results suggest that NGP can be used as a screening tool and thresholds could be defined for achieving high diagnostic yields in ES. Training the artificial intelligence (AI) with additional cases of the same ethnicity might further increase the positive predictive value of GestaltMatcher.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Síndrome de Cornelia de Lange Límite: Child / Child, preschool / Female / Humans / Infant / Male País/Región como asunto: Africa Idioma: En Revista: Am J Med Genet A Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Síndrome de Cornelia de Lange Límite: Child / Child, preschool / Female / Humans / Infant / Male País/Región como asunto: Africa Idioma: En Revista: Am J Med Genet A Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos