Autosomal dominant familial acanthosis nigricans caused by a C-terminal nonsense mutation of FGFR3.
J Hum Genet
; 66(8): 831-834, 2021 Aug.
Article
en En
| MEDLINE
| ID: mdl-33580140
ABSTRACT
FGFR3 encodes a transmembrane receptor tyrosine kinase that has six autophosphorylation sites of tyrosine. Among them, Y770 is a negative regulatory site for the downstream signaling of FGFR3. Constitutive active mutations in FGFR3 are involved in human developmental disorders including familial acanthosis nigricans, an autosomal dominant disorder characterized by general hyperpigmentation with mild acanthosis of the epidermis. Here, we report two unrelated cases of familial acanthosis nigricans with a heterozygous c.2302G>T (p.E768*) mutation in FGFR3 (NM_000142.5). FGFR3 mRNA purified from the skin lesion neither showed aberrant splicing nor nonsense-mediated mRNA decay, indicating that the FGFR3 mutant simply lacked the C-terminal 768-806 amino acids including Y770. While all of the known pathogenic mutations were missense mutations in FGFR3 showing autosomal dominant trait, the c.2302G>T mutation of FGFR3 is a unique autosomal dominant nonsense mutation that causes familial acanthosis nigricans probably via loss of negative regulatory autophosphorylation site of FGFR3.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Mutación Missense
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Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos
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Acantosis Nigricans
Tipo de estudio:
Prognostic_studies
Límite:
Child, preschool
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Female
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Humans
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Infant
Idioma:
En
Revista:
J Hum Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón