Extending the PAX1 spectrum: a dominantly inherited variant causes oculo-auriculo-vertebral syndrome.
Eur J Hum Genet
; 30(10): 1178-1181, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-35879406
ABSTRACT
Oculo-auriculo-vertebral syndrome (OAVS) is a clinically heterogeneous disorder, with both genetic and environmental contributors. Multiple genes have been associated with OAVS and common molecular pathways, such as retinoic acid and the PAX-SIX-EYA-DACH (PSED) network, are being implicated in the disease pathophysiology. Biallelic homozygous nonsense or hypomorphic missense mutations in PAX1 cause otofaciocervical syndrome type 2 (OTFCS2), a similar but more severe multi-system disorder that can be accompanied by severe combined immunodeficiency due to thymic aplasia. Here we have identified a multi-generational family with mild features of OAVS segregating a heterozygous frameshift in PAX1. The four base duplication is expected to result in nonsense-mediated decay, and therefore cause a null allele. While there was full penetrance of the variant, expressivity of facial and ear features were variable. Our findings indicate there can be monoallelic and biallelic disorders associated with PAX1, and further implicate the PSED network in OAVS.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunodeficiência Combinada Severa
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Fatores de Transcrição Box Pareados
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Síndrome de Goldenhar
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article