DLX homeobox genes are mammalian homologs of theDrosophila Distal-less (DLL) gene and consist of six genes that are divided into Dlx1/2,Dlx5/6, and Dlx3/7 bi-gene clusters. DLX5 gene encodes a transcriptional factor protein which is expressed mainly in early embryonic development and has an important role in limb, craniofacial and head development and sensory organ morphogenesis. It also has an important role in regulating the development of γ-aminobutyric acid (GABA)-ergic neurons.
Defects in this protein are the cause of split-hand/foot malformation 1 with sensorineural hearing loss, an autosomal recessive disease characterized by limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals.
The DLX5 gene is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7. It spans 4.71 kb with 3 coding exons, and its encoded protein comprises 289 amino acids. Mutations within this gene have been found in patients with split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive.
See: [Yemen>Shamseldin et al., (2012)]
Shamseldin et al. (2012) performed autozygome analysis and exom sequencing to study a Yemeni consanguineous family with autosomal recessive split hand and foot malformation in Saudi Arabia. The first patient was a 6 year old girl, who had severe limb defects noted at birth. She suffered from hearing loss. She had mild synophrys and low anterior hair line. There was dorsalisation of the palms, tapered fingers and circumferential nails, and asymmetric short and severely deformed legs and feet. There was mild scoliosis also restriction of joint flexion at all the metacarpophalangeal and interphalangeal joint. The parents were first cousins and had two affected children and several other affected relatives. One of the affected children died at the age of 7 years. The second 4 year old girl also suffered from hearing loss. She had mild frontal bossing and high frontal hair line, severe asymmetric claw-like deformity. The right hand had an elongated ebducted thumb, wide fused ring and middle fingers, and an absent index finger. AnA533C novel missense mutation was identified in exon 2 of the DLX5 gene in all affected members, and was not identified in 192 ethnically matched controls or the Exome Variant Server. This mutation affects a highly conserved residue across all species.