Faculty of Health Science
Degree of Master of Science in Human Genetics
9809684w / Lipoid proteinosis (LP) (OMIM 247100) is a rare autosomal recessive disorder that is
caused by mutations within the extracellular matrix protein 1 gene (ECM1). The ECM1
gene has been shown to play a role in angiogenesis and connective tissue matrix
generation, especially in skin and bone. The role of ECM1 in normal skin development
and maintenance is further highlighted by its role in LP and in lichen sclerosis where
autoantibodies are raised against ECM1.
LP usually presents in the first year of life with a faint or hoarse cry and is due to a
hyaline-like material deposited in the mucous membranes of the vocal cords. Gradually
(over years) there is diffuse skin infiltration and general skin thickening with a yellow,
waxy appearance. There is excessive scarring with scars often appearing at sites of minor
injury or stress. In many cases, the eyelids show typical beaded papules. In some cases,
calcification of certain aspects of the temporal lobes have been observed, and may or may
not be associated with variable neurological, psychiatric and neuropsychological
sequelae. Although the prevalence of LP in South Africa is unknown, the
disproportionately high number of case reports originating from South Africa indicates
that LP is unusually common in certain South African populations, most notably the
Coloured population of Namaqualand and the Afrikaans-speaking White population. This
may be due to a possible LP founder effect that occurred early during the European
colonisation of South Africa.
The founder effect was investigated in the South African LP patients by conducting
ECM1 mutation and linked marker analysis. The data supported a LP founder effect as
the Q276X mutation in exon seven of ECM1 was present in the homozygous state in all
LP patients investigated. In addition, the Q276X mutation was associated with a single
founder haplotype of 19-12-23-22 (ND1-D1S2343-D1S305-D1S2624). These markers
were in significant linkage disequilibrium with each other and with the Q276X mutation.
VI
As variation within ECM1 may alter properties of skin such as healing and scar
formation, ECM1 exons two through five and the first part of exon six were investigated
for nucleotide variation using denaturing high performance liquid chromatography
(dHPLC) and direct DNA sequencing in three different South African populations. Eight
nucleotide variants were identified, of which six were cytosine to thymine transitions.
Seven of the eight variants identified were either intronic or synonymous, with one
variant being a missense variant, changing a methionine residue to a threonine residue
(T130M).
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/1908 |
| Date | 20 November 2006 |
| Creators | van Hougenhouck-Tulleken, George, Wesley |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 2278871 bytes, application/pdf, application/pdf |
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