FAT4 Gene

The FAT4 gene (FAT4 stands for " FAT Atypical Cadherin 4") is a protein coding gene located at chromosome 4q28.1.

The protein encoded by the FAT4 gene is a member of the protocadherin family. Alternatively spliced transcript variants have been identified for this gene.

Cadherins are calcium-dependent cell adhesion proteins. The encoded protein plays a role in maintaining planar cell polarity and in inhibiting YAP1-mediated proliferation and differentiation of neuroprogenitor cells. Studies in mice suggest that loss of PCP signaling can cause cystic kidney disease.

Diseases associated with FAT4 include:

• Van Maldergem syndrome 2

and

• Hennekam lymphangiectasia-lymphoedema syndrome 2 (Alders M et al 2014). Hennekam's lymphangiectasia-lymphoedema syndrome is an autosomal recessive inherited disorder characterized by generalized lymphoid dysplasia affecting various organs, including the intestinal tract, pericardium, and limbs. Other features of the disorder include facial dysmorphism and cognitive impairment (Alders et al. 2014).

The phenotype "Hennekam lymphangiectasia lymphedema syndrome" is characterized by genetic heterogeneity.

• Mutations in the CCBE1 gene cause Hennekam lymphangiectasia lymphedema syndrome type1 (HKLL type1; Connell F et al. 2010).
• Mutations in the FAT4 gene (612411) cause HKLLS type2 ;
• Mutations in the ADAMTS3 gene (605011) on chromosome 4q13 cause HKLLS type3 (618154).

1. Al-Gazali LI et al. (2003) Further delineation of Hennekam syndrome. Clin Dysmorph 12: 227-232.
2. Alders M et al. (2014) Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. Hum Genet 133: 1161-1167.
3. Alders M et al (2009) Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nature Genet 41: 1272-1274.
4. Connell F et al (2010) Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia. Hum Genet 127: 231-241.
5. Hennekam RCM et al (1989) Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. Am J Med Genet 34: 593-600.