Case report: Disease phenotype associated with simultaneous biallelic mutations in ABCA4 and USH2A due to uniparental disomy of chromosome 1
Por:
Villafuerte-De la Cruz, R., Chacon-Camacho, O. F., Rodriguez-Martinez, A. C., Xilotl-De Jesus, N., Arce-Gonzalez, R., Rodriguez-De la Torre, C., Valdez-Garcia, J. E., Rojas-Martinez, A., Zenteno, J. C.
Publicada:
16 ago 2022
Resumen:
Inherited retinal diseases (IRDs) represent a spectrum of clinically and
genetically heterogeneous disorders. Our study describes an IRD patient
carrying ABCA4 and USH2A pathogenic biallelic mutations as a result of
paternal uniparental disomy (UPD) in chromosome 1. The proband is a
9-year-old girl born from non-consanguineous parents. Both parents were
asymptomatic and denied family history of ocular disease. Clinical
history and ophthalmologic examination of the proband were consistent
with Stargardt disease. Whispered voice testing disclosed moderate
hearing loss. Next-generation sequencing and Sanger sequencing
identified pathogenic variants in ABCA4 (c.4926C > G and
c.5044_5058del) and USH2A (c.2276G > T). All variants were present
homozygously in DNA from the proband and heterozygously in DNA from the
father. No variants were found in maternal DNA. Further analysis of
single nucleotide polymorphisms confirmed paternal UPD of chromosome 1.
This is the first known patient with confirmed UPD for two recessively
mutated IRD genes. Our study expands on the genetic heterogeneity of
IRDs and highlights the importance of UPD as a mechanism of autosomal
recessive disease in non-consanguineous parents. Moreover, a long-term
follow-up is essential for the identification of retinal features that
may develop as a result of USH2A-related conditions.
Filiaciones:
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico
Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City, Mexico
Genetics Department, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico
Department of Ophthalmology, University Hospital and Faculty of Medicine, Autonomous University of Nuevo Leon (UANL), Monterrey, Mexico
Institute for Obesity Research, Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico
Biochemistry Department, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Mexico City, Mexico
Tecnol Monterrey, Escuela Med & Ciencias Salud, Monterrey, Mexico
Univ Nacl Autonoma Mex, Fac Estudios Super Iztacala, Carrera Med Cirujano, Mexico City, Mexico
Inst Ophthalmol Conde Valenciana, Genet Dept, Mexico City, Mexico
Univ Hosp, Autonomous Univ Nuevo Leon UANL, Fac Med, Dept Ophthalmol, Monterrey, Mexico
(Corresponding Author), Tecnol Monterrey, Escuela Med & Ciencias Salud, Monterrey, Mexico
(Corresponding Author), Tecnol Monterrey, Escuela Med & Ciencias Salud, Inst Obes Res, Monterrey, Mexico
Tecnol Monterrey, Escuela Med & Ciencias Salud, Inst Obes Res, Monterrey, Mexico
Natl Autonomous Univ Mex UNAM, Fac Med, Biochem Dept, Mexico City, Mexico
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