Two De Novo Mosaic Variants Within the Same Site of PHEX Gene in a Girl with X-Linked Hypophosphatemic Rickets.
Calcif Tissue Int
; 110(2): 266-271, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34487203
ABSTRACT
X-linked hypophosphatemic rickets (XLH) is the most common form of hypophosphatemic rickets, which is caused by the deficiencies of PHEX gene with an X-linked dominant inheritance pattern. As at least several thousands of XLH patients have been diagnosed, only several males and fewer females with mosaicism of PHEX gene were found. Here we describe an XLH girl with two de novo mosaic variants within the same site of PHEX gene. To rapidly screen all of the causative genes of hypophosphatemic rickets and rule out other diseases, DNA samples were initially analyzed using whole exome sequencing (WES). Interestingly, two different pathogenic mosaic variants, a known c.1809G > A(p.W603*) variant and a novel c.1809G > T(p.W603C) variant within the same site of PHEX gene, were identified in the proband by WES. Subsequent Sanger sequencing confirmed the presence and de novo pattern of these two mosaic variants in the proband, which were absent in her healthy parents. This is the first case to report two different mosaic variants of PHEX gene in an XLH individual. This XLH girl has a de novo mosaic genotype of c.1809 = /G > T/G > A in PHEX gene. Our report adds an unusual mocaicism case for XLH and expands the mutational event and spectrum of PHEX gene. Our report also alerts clinicians and geneticists to be cautious about mocaicism and detection methods.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças Genéticas Ligadas ao Cromossomo X
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Raquitismo Hipofosfatêmico Familiar
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Endopeptidase Neutra Reguladora de Fosfato PHEX
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article