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. Hennekam

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1161-1167
Number of pages7
JournalHuman Genetics
Volume133
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Fingerprint Dive into the research topics of 'Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome'. Together they form a unique fingerprint.

Cite this