Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report.
BMC Med Genet
; 19(1): 80, 2018 05 16.
Article
em En
| MEDLINE
| ID: mdl-29769041
ABSTRACT
BACKGROUND:
Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG, encoding the three different polypeptide chains that comprise fibrinogen. Neurodevelopmental abnormalities have not been associated with fibrinogen deficiencies. In this study, we report an unusual patient with a combination of two independently inherited genetic conditions; fibrinogen deficiency and early onset cortical atrophy. CASE PRESENTATION The study describes a male child from consanguineous family presented with hypofibrinogenemia, diffuse cortical atrophy, microcephaly, hypertonia and axonal motor neuropathy. Through a combination of homozygosity mapping and exome sequencing, we identified bi-allelic pathogenic mutations in two genes a homozygous novel truncating mutation in FGG (c.554del; p.Lys185Argfs*14) and a homozygous missense mutation in TBCD (c.1423G > A;p.Ala475Thr). Loss of function mutations in FGG have been associated with fibrinogen deficiency, while the c.1423G > A mutation in TBCD causes a novel syndrome of neurodegeneration and early onset encephalopathy.CONCLUSIONS:
Our study highlights the importance of homozygosity mapping and exome sequencing in molecular prenatal diagnosis, especially when multiple gene mutations are responsible for the phenotype.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrinogênio
/
Córtex Cerebral
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Afibrinogenemia
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Proteínas Associadas aos Microtúbulos
Tipo de estudo:
Prognostic_studies
Limite:
Child, preschool
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Humans
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Male
Idioma:
En
Revista:
BMC Med Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos