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Human Genetics

, Volume 133, Issue 9, pp 1161–1167 | Cite as

Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome

  • Mariëlle Alders
  • Lihadh Al-Gazali
  • Isabelle Cordeiro
  • Bruno Dallapiccola
  • Livia Garavelli
  • Beyhan Tuysuz
  • Faranak Salehi
  • Martin A. Haagmans
  • Olaf R. Mook
  • Charles B. Majoie
  • Marcel M. Mannens
  • Raoul C. HennekamEmail author
Original Investigation

Abstract

The Hennekam lymphangiectasia–lymphedema syndrome is a genetically heterogeneous disorder. It can be caused by mutations in CCBE1 which are found in approximately 25 % of cases. We used homozygosity mapping and whole-exome sequencing in the original HS family with multiple affected individuals in whom no CCBE1 mutation had been detected, and identified a homozygous mutation in the FAT4 gene. Subsequent targeted mutation analysis of FAT4 in a cohort of 24 CCBE1 mutation-negative Hennekam syndrome patients identified homozygous or compound heterozygous mutations in four additional families. Mutations in FAT4 have been previously associated with Van Maldergem syndrome. Detailed clinical comparison between van Maldergem syndrome and Hennekam syndrome patients shows that there is a substantial overlap in phenotype, especially in facial appearance. We conclude that Hennekam syndrome can be caused by mutations in FAT4 and be allelic to Van Maldergem syndrome.

Keywords

Lymphedema Intellectual Disability Planar Cell Polarity Hippo Pathway Homozygosity Mapping 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

439_2014_1456_MOESM1_ESM.doc (1.3 mb)
Supplementary material 1 (DOC 1380 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mariëlle Alders
    • 1
  • Lihadh Al-Gazali
    • 2
  • Isabelle Cordeiro
    • 3
  • Bruno Dallapiccola
    • 4
  • Livia Garavelli
    • 5
  • Beyhan Tuysuz
    • 6
  • Faranak Salehi
    • 1
  • Martin A. Haagmans
    • 1
  • Olaf R. Mook
    • 1
  • Charles B. Majoie
    • 7
  • Marcel M. Mannens
    • 1
  • Raoul C. Hennekam
    • 1
    • 8
    Email author
  1. 1.Department of Clinical Genetics, Academic Medical CentreUniversity of AmsterdamAmsterdamNetherlands
  2. 2.Department of PediatricsUnited Arab Emirates UniversityAl-AinUnited Arab Emirates
  3. 3.Serviço de GenéticaHospital Santa MariaLisbonPortugal
  4. 4.Ospedale Pediatrico Bambino GesùIRCCSRomeItaly
  5. 5.Istituto di Rocivero e Cra a Carattere Scientifico, Arcispedale S. Maria NuovaReggio EmiliaItaly
  6. 6.Department of Pediatric Genetics, Cerrahpasa Medical SchoolIstanbul UniversityIstanbulTurkey
  7. 7.Department of Radiology, Academic Medical CentreUniversity of AmsterdamAmsterdamNetherlands
  8. 8.Department of Pediatrics H7-236, Academic Medical CentreUniversity of AmsterdamAmsterdamNetherlands

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