The E37X is a common HMGCL mutation in Portuguese patients with 3-hydroxy-3-methylglutaric CoA lyase deficiency

Ten novelHMGCLmutations in 24 patients of different origin with 3-hydroxy-3-methyl-glutaric aciduria

“…This mutation was also found in an Argentinian patient of Spanish ancestry and in one Moroccoan; and since the other studied Moroccoan patient carries it , the Mediterranean mutation may have a high incidence in that country. The present study also demonstrates that the mutation c.504_505delCT is the third most frequent worldwide although its incidence is much lower than the first two, and it seems to be exclusively located in the Iberian Peninsula, where 15% of Portuguese (2 cases) (Cardoso, et al, 2004) and 27% of Spanish patients have it . In spite of genetic similarities between the Iberian Peninsula populations, the Portuguese seem to be more homogeneous, bearing only one of these two mutations.…”

HMG–CoA Lyase Deficiency

“…The third most frequent mutation is c.504_505delCT (11 alleles, 10 patients: 1 homozygous, 9 double heterozygous), although its incidente is much lower than the first two. It seems to be exclusively located in the Iberian Peninsula, where 15% of Portuguese (2 cases) (Cardoso et al, 2004) and 27% of Spanish patients have it (Menao et al, 2009). This mutation is also present in 3 of the 4 molecularly diagnosed Brazilians patients, though they were of Portuguese origin (Vargas et al, 2007).…”

“…Position refers to the numbering of the HL cDNA sequence in Mitchell et al, 1993. ht, heterozygous The second most frequent mutation is the c.109G>T (Mediterranean mutation) (55 alleles, 31 patients: 24 homozygous, 6 double heterozygous, 1 heterozygous with an allele unknown), found mostly in the Iberian Peninsula (13 patients in Portugal, 11 in Spain and 3 in brazilianportugueses). It has also been described two cases in Morocco and another in Turkey (Pié et al, 1997;Casale et al, 1998;Cardoso et al, 2004;Puisac et al, 2005;Menao et al, 2009). It has been hypothesized that in Portugal and Spain the genetic hit was introduced during the Arabian invasions of the Iberian Peninsula in the eighth century.…”

Recurrent mutation in the HMGCL gene in a family segregating HMG-CoA lyase deficiency

“…The HMGCL gene produces two isoforms; isoform A is expressed in mitochondria and isoform B is found in peroxisomes (Menao et al, 2009). HMGCLD is rare in Europe and Japan, but a common inherited disease in Saudi Arabia and Portugal (Cardoso et al, 2004;Ozand et al, 1992;Funghini et al, 2001). HMG CoA lyase deficiency has been extensively studied and over 30 mutations in the HMGCL gene have been reported (Cardoso et al, 2004;Menao et al, 2009).…”

“…HMGCLD is rare in Europe and Japan, but a common inherited disease in Saudi Arabia and Portugal (Cardoso et al, 2004;Ozand et al, 1992;Funghini et al, 2001). HMG CoA lyase deficiency has been extensively studied and over 30 mutations in the HMGCL gene have been reported (Cardoso et al, 2004;Menao et al, 2009). In Saudi Arabia, 89% of patients have a missense mutation in exon 2 (122G>A; R41Q) (Ozand et al, 1991(Ozand et al, , 1992.…”