Neurological Sciences

, Volume 35, Issue 1, pp 91–93 | Cite as

Homozygosity and severity of phenotypic presentation in a CADASIL family

  • Claudia Vinciguerra
  • Alessandra Rufa
  • Silvia Bianchi
  • Antonio Sperduto
  • Monica De Santis
  • Alessandro Malandrini
  • Maria Teresa Dotti
  • Antonio Federico
Brief Communication

Abstract

Most of causative mutations of the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are missense point mutations either creating or deleting one cysteine residue, inherited in a heterozygous state. Only few homozygous patients are reported to date and some of them showed phenotypic peculiarities. We here describe a CADASIL family in which a member showed homozygous mutation and compare its clinical profile with five subjects throughout three generation of the pedigree, carrying the same mutation in heterozygosity. The index patient was a 44-year-old Italian man, born from consanguineous parents (first cousins). Symptoms started at 23 years and progressing with recurrent ischemic stroke episode. Diffuse leukoencephalopathy and a severe cognitive impairment were evident, GOMs were detected in skin specimens and a homozygous p.Cys183Ser mutation of the NOTCH3 gene was found. Among the other five heterozygous relatives for the same mutation, both parents developed stroke in advanced age and all the others were clinically asymptomatic. We discuss these findings in relationship to previous data from the literature in CADASIL and in other dominant neurological disorders.

Keywords

CADASIL Homozygosity Early onset GOMs 

Notes

Acknowledgments

Research in part supported by a grant from Ministry of Health and Tuscany Region (“Evaluation of Notch3 mutations” 2009 and “Investigations on MCI”. resolution n.78-01/03/1 1) to AF and a grant from the Ministry of University to MTD.

Conflict of interest

All authors declare no conflict of interest.

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Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  • Claudia Vinciguerra
    • 1
  • Alessandra Rufa
    • 1
  • Silvia Bianchi
    • 1
  • Antonio Sperduto
    • 1
  • Monica De Santis
    • 1
  • Alessandro Malandrini
    • 1
  • Maria Teresa Dotti
    • 1
  • Antonio Federico
    • 1
  1. 1.Department of Medicine, Surgery and NeurosciencesUniversity of SienaSienaItaly

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