Abstract
Classical citrullinemia type I (CTLN1) is an autosomal recessive disorder encoded by the ASS1 gene, which codes for argininosuccinate synthetase (ASS), the rate-limiting enzyme in the urea cycle. Previously, we identified the mutation p.G390R in patients with CTLN1 in the San Luis Province of Argentina. Here, we report the results of p.G390R analysis in a larger number of probands, relatives of involved families and additionally, a population study to identify carriers. Altogether, we analyzed 420 alleles, belonging to 12 probands, 26 relatives, and 172 healthy volunteers. All the probands were homozygous for the mutation, and 21 of 26 relatives were carriers. The occurrence of the disease in descendants of couples at risk was 57% showing a preferential transmission of the mutant allele compared to the normal allele. The carrier frequency in the general San Luis Province population was 4.1%, suggesting the incidence of CTLN1 to be 1:2,427, which is approximately 20 times higher than for the general population. This work suggests that there should be an increased awareness of preconceptual screening of CTNL1 among individuals/couples who are at risk in the San Luis Province in order to better inform them of their reproductive options.
Cascade/family and population molecular screening for carrier identification were performed in an Argentinean province with high incidence of CTLN1, a first step to preconceptional screening.
Competing interests: None declared
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References
ACOG Committee on Genetics (2009) ACOG Committee Opinion No. 442: preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstet Gynecol 114:950–953
Appelbe W, Auerbach AD, Becker K et al (2007) Recommendations of the 2006 Human Variome Project meeting. Nat Genet 39(4):433–436
Brusilow SW, Horwich AL (2001) Urea cycle enzymes. In: Scriver C, Beaudet A, Valle D, Sly W (eds) Metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 1909–1963
Engel K, Höhne W, Häberle J (2009) Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene. Hum Mut 30(3):300–307
Godard B, ten Kate L, Evers-Kiebooms G, Aymé S (2003) Population genetic screening programmes: principles, techniques, practices, and policies. Eur J Hum Genet 11:S49–S87
Kaback M, O’Brien J (1973) Tay–Sachs: prototype for prevention of genetic disease. In: McKusic V, Claiborne R (eds) Medical genetics. HP Publishing, New York, pp 253–262
Kaback MM (2000) Population-based genetics screening for reproductive counseling: the Tay–Sachs experience. Eur J Pers 159:S192–S195
Kleijer WJ, Garritsen VH, van der Sterre MLT, Berning C, Häberle J, Huijmans JGM (2006) Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia. Prenat Diagn 26(3):242–247
Laróvere LE, Angaroni CJ, Antonozzi SL, Shimohama M, de Kremer RD (2009) Citrullinemia type I, classical variant. Identification of ASS-p.G390R (c.1168G>A) mutation in families of a limited geographic area of Argentina: a possible population cluster. Clin Biochem 42(10/11):1166–1168
McMurray WC, Mohyuddin F, Rossiter RJ et al (1962) Citrullinuria, a new aminoaciduria associated with mental retardation. Lancet 1:138
Acknowledgements
The authors gratefully acknowledge Prof. Dr. Antonio Blanco and Dr. Marshall Summar for the critical readings of the manuscript. We also thank the patients’ families and the volunteers from Villa Mercedes for their cooperation and the technical assistance of María Fernanda Santi. This study was supported partially by grants from SECYT (No. 214/10) and FONCYT (PICT 05, No. 5-34226) and Innovative Medicines Company, Argentina.
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Communicated by: Verena Peters
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Laróvere, L.E., Ruiz, S.M.S., Angaroni, C.J., de Kremer, R.D. (2012). Molecular Epidemiology of Citrullinemia Type I in a Risk Region of Argentina: A First Step to Preconception Heterozygote Detection. In: JIMD Reports - Case and Research Reports, 2012/3. JIMD Reports, vol 6. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_127
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DOI: https://doi.org/10.1007/8904_2012_127
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