Published in Lab Times 05-2011.
An Isreali team pinpoints a mutation causing a very rare disorder.
With a burgeoning rise in security measures and migration rules, it is hard to evade the immigration personnel when traveling to new places. But what if one cannot fulfill the requirements for a biometric scan due to a mere absence of fingerprints?
An extremely rare congenital disorder called ‘adermatoglyphia’ (ADG) exhibits exactly this condition and is metaphorically described as the ‘immigration delay disease’. The Israeli scientist Eli Sprecher and colleagues at the Tel Aviv University together with researchers at the University Hospital Basle, Switzerland have recently identified a pathological point mutation causing ADG (Am J Hum Genet, 89(2), 302-7).
‘Dermatoglyphs’ refer to the epidermal ridges on the skin on fingers, palms, toes and soles. Fingerprints are the dermatoglyphs on the finger tips and have been
unanimously used to ascertain identity, owing to the fact that once developed embryonally, at about 24 weeks post-fertilization, they do not undergo any modification throughout life. Initially thought to enhance friction to enable grasping, their physiological role has remained controversial. Recent reports suggest that fingerprints may serve to amplify vibratory signals to deeply embedded nerves in fine texture perception. ADG affects to-date only four families. Besides the lack of fingerprints, three of four patients have additional ‘symptoms’ including facial milk spots, skin blisters or reduced sweat glands.
The Sprecher group investigated a large Swiss kindred presenting with autosomal dominant adermatoglyphia. Multipoint linkage analysis and haplotype analysis with polymorphic markers revealed a heterozygous stretch of DNA on the chromosomal region 4q22, unique to the patients. On further analysis, they were able to pin down the locus to SMARCAD1, a gene that encodes a protein structurally related to the SWI2/SNF2 superfamily of DNA-dependent ATPases in chromatin remodelling complexes. The SMARCAD1 gene product is thought to be a regulator of transcriptional activity and one of the two isoforms of the gene has been shown to be skinspecific. The group identified a pathological G>T transversion in the first intron of the skin-specific variant and confirmed the segregation of the mutation with the disease phenotype in the Swiss family, in comparison to healthy subjects. The group then mapped the consequences of the mutation and, using in vitro approaches, showed that the polymorphism in fact eliminated an essential donor splice site in the primary transcript, resulting in aberrant splice variants. The aberrant products arising from cryptic splice sites are plausibly degraded and, hence, not detected in the patient fibroblasts.
In conclusion, the work of the Isreali-Swiss group offers a molecular explanation to the pathology of ADG and attributes a point mutation in SMARCAD1 to the development of the disorder. Full-length SMARCAD1 has a well-described role in controlling the expression of several genes, ranging from transcriptional factors and histone modifiers to regulators of the cell cycle and development. Unidentified SMARCAD1 targets may thus function in dermatoglyph and sweat gland development. Their study bolsters the fact that rare monogenic traits represent an invaluable tool to study unknown aspects of biology and single gene polymorphisms in introns can affect even the most intricate patterning of the human skin.
Photo: 38-365 Fingerprint by Bram Cymet via Creative Commons License