Uncovering Low-Level Maternal Gonosomal Mosaicism in X-Linked Agammaglobulinemia : Implications for Genetic Counseling
Rivière, Jacques G.. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Franco-Jarava, Clara (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martínez Gallo, Mónica (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Aguiló-Cucurull, Aina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Blasco-Pérez, Laura (Hospital Universitari Vall d'Hebron)
Paramonov, Ida (Hospital Universitari Vall d'Hebron)
Antolín, María (Hospital Universitari Vall d'Hebron)
Martín-Nalda, Andrea (Jeffrey Model Foundation Excellence Center)
Soler-Palacín, Pere (Jeffrey Model Foundation Excellence Center)
Colobrán Oriol, Roger (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	X-linked agammaglobulinemia (XLA) is a clinically and genetically well-defined immunodeficiency and the most common form of agammaglobulinemia. It is characterized by susceptibility to recurrent bacterial infections, profound hypogammaglobulinemia, and few or no circulating B cells. XLA is caused by mutations in the BTK gene, which encodes Bruton's tyrosine kinase (BTK). Because of its X-linked recessive inheritance pattern, XLA virtually only affects males, and the mother is the carrier of the mutation in 80-85% of the males with this condition. In the remaining 15-20% of the cases, the affected male is considered to have a de novo mutation. Here, we present the case of a child with a diagnosis of XLA caused by a missense mutation in the BTK gene (c. 494G>A/p. C165Y). Apparently, his mother was wild type for this gene, which implied that the mutation was de novo, but careful analysis of Sanger electropherograms and the use of high-coverage massive parallel sequencing revealed low-level maternal gonosomal mosaicism. The mutation was detected in various samples from the mother (blood, urine, buccal swab, and vaginal swab) at a low frequency of 2-5%, and the status of the patient's mutation changed from de novo to inherited. This study underscores the importance of accurately establishing the parents' status on detection of an apparently de novo mutation in a patient, as inadvertent low-level mosaicism may lead to misinterpretation of the risk of recurrence, vital for genetic counseling.
Ajuts:	Ministerio de Economía y Competitividad PI14/00405 Instituto de Salud Carlos III PI17/00660
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	X-linked agammaglobulinemia (XLA) ; Bruton agammaglobulinemia ; Gonosomal mosaicism ; Genetic counseling ; BTK mutation
Publicat a:	Frontiers in immunology, Vol. 11 (february 2020) , ISSN 1664-3224

DOI: 10.3389/fimmu.2020.00046
PMID: 32117230

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