Abstract
An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabí. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabí. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabí could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.
Highlights
Inherited ichthyosis is a group of keratinization disorders characterized by generalized hyperkeratosis and scaling
In Galicia (Northwestern Spain), three founder mutations, c.2278C > T, c.1223_1227delACAC and c.984 + 1G > A, account for the majority of all TGM1 mutations identified in this Spanish region[6]
A visual inspection of the haplotypes represented in Table 2 allow us to roughly differentiate two main groups by focusing in the two 5′-STRs that are close to the mutation: one group share the D14S581-D14S64 haplotype 2–5, while the other group share the haplotype 3–8; both haplotypes accounting for 18 out of 20 haplotypes
Summary
Inherited ichthyosis is a group of keratinization disorders characterized by generalized hyperkeratosis and scaling. These diseases are divided into two groups, syndromic ichthyosis and non-syndromic ichthyosis, according to the presence or absence of extracutaneous findings, respectively. Lamellar ichthyosis is the most common type of ARCI; some of its clinical manifestations include: generalized scaling, ectropion, eclabium, collodion membrane at birth and palmoplantar keratoderma[2]. TGM14, is the most commonly mutated gene in LI. It encodes the transglutaminase 1 enzyme that is involved in the formation of the cornified cell envelope of the epidermis[2]. A few founder mutations have been described in the TGM1 gene. In Galicia (Northwestern Spain), three founder mutations, c.2278C > T, c.1223_1227delACAC and c.984 + 1G > A, account for the majority of all TGM1 mutations identified in this Spanish region[6]
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