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Homozygous loss of function BRCA1 variant causing a Fanconi-anemia-like phenotype, a clinical report and review of previous patients.
Freire, Bruna L; Homma, Thais K; Funari, Mariana F A; Lerario, Antônio M; Leal, Aline M; Velloso, Elvira D R P; Malaquias, Alexsandra C; Jorge, Alexander A L.
Afiliación
  • Freire BL; Unidade de Endocrinologia Genética (LIM25) e Laboratório de Endocrinologia Celular e Molecular, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular (LIM42),
  • Homma TK; Unidade de Endocrinologia Genética (LIM25) e Laboratório de Endocrinologia Celular e Molecular, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular (LIM42),
  • Funari MFA; Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular (LIM42), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Lerario AM; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA.
  • Leal AM; Laboratorio de Citogenetica, Unidade de Hematologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Velloso EDRP; Laboratorio de Citogenetica, Unidade de Hematologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Malaquias AC; Unidade de Endocrinologia Genética (LIM25) e Laboratório de Endocrinologia Celular e Molecular, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Unidade de Endocrinologia Pediatrica, Departamento de Pediatria, Irmandade da Santa Casa de Misericó
  • Jorge AAL; Unidade de Endocrinologia Genética (LIM25) e Laboratório de Endocrinologia Celular e Molecular, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular (LIM42),
Eur J Med Genet ; 61(3): 130-133, 2018 Mar.
Article en En | MEDLINE | ID: mdl-29133208
BACKGROUND: Fanconi Anemia (FA) is a rare and heterogeneous genetic syndrome. It is associated with short stature, bone marrow failure, high predisposition to cancer, microcephaly and congenital malformation. Many genes have been associated with FA. Previously, two adult patients with biallelic pathogenic variant in Breast Cancer 1 gene (BRCA1) had been identified in Fanconi Anemia-like condition. CLINICAL REPORT: The proband was a 2.5 year-old girl with severe short stature, microcephaly, neurodevelopmental delay, congenital heart disease and dysmorphic features. Her parents were third degree cousins. Routine screening tests for short stature was normal. METHODS: We conducted whole exome sequencing (WES) of the proband and used an analysis pipeline to identify rare nonsynonymous genetic variants that cause short stature. RESULTS: We identified a homozygous loss-of-function BRCA1 mutation (c.2709T > A; p. Cys903*), which promotes the loss of critical domains of the protein. Cytogenetic study with DEB showed an increased chromosomal breakage. We screened heterozygous parents of the index case for cancer and we detected, in her mother, a metastatic adenocarcinoma in an axillar lymph node with probable primary site in the breast. CONCLUSION: It is possible to consolidate the FA-like phenotype associated with biallelic loss-of-function BRCA1, characterized by microcephaly, short stature, developmental delay, dysmorphic face features and cancer predisposition. In our case, the WES allowed to establish the genetic cause of short stature in the context of a chromosome instability syndrome. An identification of BRCA1 mutations in our patient allowed precise genetic counseling and also triggered cancer screening for the patient and her family members.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteína BRCA1 / Predisposición Genética a la Enfermedad / Anemia de Fanconi / Homocigoto / Mutación Tipo de estudio: Prognostic_studies Límite: Child, preschool / Female / Humans / Male Idioma: En Revista: Eur J Med Genet Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteína BRCA1 / Predisposición Genética a la Enfermedad / Anemia de Fanconi / Homocigoto / Mutación Tipo de estudio: Prognostic_studies Límite: Child, preschool / Female / Humans / Male Idioma: En Revista: Eur J Med Genet Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article