Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report

BMC Medical Genetics
Joshi StephenMay Christine V Malicdan

Abstract

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. 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 on...Continue Reading

References

Jan 1, 1997·Annual Review of Cell and Developmental Biology·A Desai, T J Mitchison
Mar 1, 2002·Advances in Protein Chemistry·N J Cowan, S A Lewis
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·M W Mosesson
Jul 21, 2006·Pathophysiology of Haemostasis and Thrombosis·Marguerite Neerman-Arbez
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jan 29, 2010·PloS One·Mónica López FanarragaJuan Carlos Zabala
Nov 4, 2010·Neurology India·Gaurav ChhabraA K Mukhopadhayay
Feb 5, 2011·Current Opinion in Genetics & Development·Max A TischfieldElizabeth C Engle
Aug 27, 2013·Methods in Cell Biology·Guoling Tian, Nicholas J Cowan
May 21, 2014·American Journal of Medical Genetics. Part a·Cathryn J PoultonGrazia M S Mancini
Feb 18, 2016·European Journal of Human Genetics : EJHG·Joshi StephenYair Anikster
Oct 27, 2016·Molecular Genetics and Metabolism·Kevin J O'BrienBernadette R Gochuico
Sep 27, 2016·American Journal of Human Genetics·Noriko MiyakeNaomichi Matsumoto

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Citations

Jun 27, 2019·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Di TianLi Shu
Jul 25, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Esra IsikFerda Ozkinay
Aug 24, 2021·Child Neurology Open·Christina M QuitmannThorsten Marquardt

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Methods Mentioned

BETA
exome sequencing
genotyping

Software Mentioned

CADD
Mutation Taster
GATK
Polyphen
SnpEff
gnomAD
SIFT

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