Clefting disorders

Gene: FOXE1

Green List (high evidence)

Clifton-Bligh et al. (1998) demonstrated that thyroid agenesis, cleft palate, and choanal atresia in 2 brothers was caused by a homozygous missense variant (A65V) in FOXE1. Mother was heterozygous and Paternal DNA was not available for analysis. The mutant protein exhibits impaired DNA binding and loss of transcriptional function.

Castanet et al. (2002) described a variant (S57N) in the FOXE1 gene in 2 male sibs, born to consanguineous parents, with congenital hypothyroidism, athyreosis, and cleft palate. Parents were heterozygous and unaffected and variant was not found in 31 unrelated cases of athyreosis or normal controls. S57N TTF-2 mutant protein showed impaired DNA binding and partial loss of transcriptional function.

In a girl, born of consanguineous Turkish parents, with Bamforth-Lazarus syndrome, Baris et al. (2006) identified homozygosity for a missense variant (R102C) affecting a highly conserved residue in FOXE1. Heterozygous parents were unaffected, and the mutation was not detected in 100 control chromosomes. R102C mutant TTF-2 protein showed loss of DNA binding and was transcriptionally inactive.

Created: 1 Feb 2021, 1:36 a.m. | Last Modified: 1 Feb 2021, 1:36 a.m.

Panel Version: 0.42

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Bamforth-Lazarus syndrome, OMIM #241850

Publications

• PubMed: 9697705, 12165566, 16882747