Expanding the clinical spectrum of the "HDAC8-phenotype" - Implications for molecular diagnostics, counselling and risk prediction - Université de Rennes Access content directly
Journal Articles Clinical Genetics Year : 2016

Expanding the clinical spectrum of the "HDAC8-phenotype" - Implications for molecular diagnostics, counselling and risk prediction

Kerstin S. Wendt
  • Function : Author
Karin Buiting
  • Function : Author
Hartmut Engels
  • Function : Author
Renata Glazar
  • Function : Author
Barbara Graffmann
  • Function : Author
Maura Masciadri
  • Function : Author
Juan Pié
  • Function : Author
Feliciano J. Ramos
  • Function : Author
Margarita Stefanova
  • Function : Author
Tim M. Strom
  • Function : Author
Jolanta Wierzba
  • Function : Author
Giuseppe Zampino
  • Function : Author
  • PersonId : 912933

Abstract

Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of eleven patients carrying ten distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS-overlapping features. The phenotype of our patients is very broad whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X-inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counselling and risk prediction

Dates and versions

hal-01255865 , version 1 (14-01-2016)

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Ilaria Parenti, Cristina Gervasini, Jelena Pozojevic, Kerstin S. Wendt, Erwan Watrin, et al.. Expanding the clinical spectrum of the "HDAC8-phenotype" - Implications for molecular diagnostics, counselling and risk prediction. Clinical Genetics, 2016, 89 (5), pp.564-573. ⟨10.1111/cge.12717⟩. ⟨hal-01255865⟩
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