Limb disorders

Gene: TFAP2B

Comment on list classification: Updated rating from Red to Green: Confirmed DD-G2P gene for Char syndrome, which includes hand anomalies. Although not all patients display a hand phenotype, there's sufficient cases for inclusion on the limb panel.

Created: 16 Oct 2018, 2:05 p.m.

Confirmed DD-G2P gene for Char syndrome (MIM:169100). Char syndrome is characterized by the triad of patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies including aplasia or hypoplasia of the middle phalanges of the fifth fingers or fifth finger clinodactyly. However, hand anomalies are not reported in all patients. Variants in TFAP2B can also cause PDA without facial dysmorphism or hand anomalies (MIM:617035).

Created: 16 Oct 2018, 12:40 p.m.

In a large 3-generation family segregating autosomal dominant Char syndrome (CHAR; 169100), Mani et al. (2005, 15684060) identified heterozygosity for a G-to-A transition at position +5 of the splice donor site of intron 3, a highly conserved nucleotide in the TFAP2B gene. Of the 22 affected members, all had clinodactyly. Chen et al (PMID:21643846) report the same variant in a Chinese family, but none of the affected individuals in the Chinese family exhibited the craniofacial or fifth-finger anomalies of Char syndrome.

Created: 16 Oct 2018, 12:22 p.m.

Zhao et al. (2001, PMID:11505339) studied 8 patients with Char syndrome and identified 4 novel variants in TFAP2B. Not all the patients showed hand anomalies. Patients who do have hand anomalies are: A Palestinian boy with clinodactyly harboured a heterozygous C-to-T transition at nucleotide 673 (R225C) in TFAP2B. Zhao also found a heterozygous C-to-A transversion at nucleotide 673 in the TFAP2B gene (p.R225S) in an English family described previously by Sweeney et al (PMID:10955477) with hand anomalies but no cardiovascular anomalies.

Created: 16 Oct 2018, 12:22 p.m.