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.
Subject(s)
Afibrinogenemia/genetics , Cerebral Cortex/pathology , Fibrinogen/genetics , Microtubule-Associated Proteins/genetics , Atrophy , Child, Preschool , Consanguinity , Homozygote , Humans , Male , Pedigree , Exome SequencingABSTRACT
Chromobacterium violaceum is a rare pathogen that can cause potentially fatal infections in humans. Till date, 150 cases are reported worldwide including 7 from India. We report a 6 month old infant who presented with high grade fever, respiratory distress and multiple vesicular skin lesions. Chromobacterium violaceum was isolated from blood, bone marrow aspirate and from skin lesions. Infant responded to treatment with piperacillin and ciprofloxacin, and is doing well on follow up.
