RESUMO
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder due to pathogenic variants in Fibrillin-1 (FBN1) affecting nearly one in every 10,000 individuals. We report a 16-month-old female with early-onset MFS heterozygous for an 11.2 kb de novo duplication within the FBN1 gene. Tandem location of the duplication was further confirmed by optical genome mapping in addition to genetic sequencing and chromosomal microarray. This is the third reported case of a large multi-exon duplication in FBN1, and the only one confirmed to be in tandem. As the vast majority of pathogenic variants associated with MFS are point mutations, this expands the landscape of known FBN1 pathogenic variants and supports consistent use of genetic testing strategies that can detect large, indel-type variants.
Assuntos
Síndrome de Marfan , Humanos , Feminino , Lactente , Fibrilina-1/genética , Mutação , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Testes Genéticos , Mutação Puntual , Fibrilinas/genética , Adipocinas/genéticaRESUMO
BACKGROUND: Reports of interstitial duplication of chromosome 20q11 are rare with only nine published patients to date. METHODS: We performed karyotype and chromosomal microarray analysis on a peripheral blood sample for our patient and reviewed the genes in the region to provide genotype-phenotype correlation. RESULTS: Clinical features of the patient include minor dysmorphic facial features, shorthands and feet, bilateral conductive hearing loss, global developmental delay, and behavioral issues with attention deficit hyperactivity disorder. Together with previously published cases of 20q11 duplication, we show that patients with overlapping duplications share a similar clinical phenotype of dysmorphic craniofacial features and developmental delay. CONCLUSION: We report an 8-year-old girl with a 9.1 Mb interstitial duplication of chromosome 20q11.22q13.11. Our observations suggest that a novel duplication syndrome and documentation of similar cases will further help clarify the phenotype.
Assuntos
Transtornos Cromossômicos/genética , Duplicação Cromossômica , Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 22/genética , Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Criança , Transtornos Cromossômicos/patologia , Anormalidades Craniofaciais/patologia , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , FenótipoRESUMO
Due to the variable presentation of mosaic chromosomal abnormalities, cases such as this are needed to define the phenotypic spectrum. It also highlights the importance of chromosome analysis to identify structural abnormalities that result in aneuploidy.