Brachydactyly Type A3 Is Caused By A Novel 13 Bp Hoxd13 Frameshift Deletion In A Chinese Family

Brachydactyly type A (BDA) is defined as short middle phalanges of the affected digits and is subdivided into four types (BDA1-4). To date, the molecular cause is unknown. However, there is some evidence that pathogenic variants ofHOXD13could be associated with BDA3 and BDA4. Here, we report a Chinese autosomal dominant BDA3 pedigree with a novelHOXD13mutation. The affected individuals presented with an obviously shorter fifth middle phalanx. The radial side of the middle phalanx was shorter than the ulnar side, and the terminal phalanx of the fifth finger inclined radially and formed classical clinodactyly. Interestingly, the index finger was normal. The initial diagnosis was BDA3. However, the distal third and fourth middle phalanges were also slightly affected, resulting in mild radial clinodactyly. Both feet showed shortening of the middle phalanges, which were fused to the distal phalanges of the second to the fifth toes, as reported in BDA4. Therefore, this pedigree had combined BDA3 and atypical BDA4. By direct sequencing, a 13 bp deletion within exon 1 ofHOXD13(NM_000523.4: c.708_720del13; NP_000514.2: p.Gly237fs) was identified. The 13 bp deletion resulted in a frameshift and premature termination of HOXD13. This study provides further evidences that variants inHOXD13cause BDA3-BDA4 phenotypes.