51
Letters to the Editor
Audrey Heimler Huntington Disease Program Depamnent of Psychiatry University of Connecticut Health Center Farmington, Connecticut
Changing the Definition of "Proband" in the New Standardized Nomenclature for Pedigrees To the Editor:
Bennett et aL (1995a) presented recommendations of the Pedigree Standardization Task Force of the National Society of Genetic Counselors. Because the article was recently reprinted in this journal (Bennett et al., Vot. 4, No. 4, 1995b), I would like to bring to attention a recent exchange of letters regarding the Bennett et al. (1995a,b) definition of "proband." Bennett et al. (1995a, Fig. 1, p. 746), define "proband" as the "first affected family member coming to medical attention." Marazita (1995) took issue with this definition and Bennett et aL (1995c) agreed. This definition illustrates the dichotomy in the use of the term "proband" by clinicians vs. researchers. Bennett et aL's (1995a) definition is the meaning that clinicians seem to have evolved (see, e.g., Thompson, et aL, 1991). Researchers, on the other hand, rely on the original use of the word "proband" (Weinberg, 1927; Morton, 1959) as an affected person who is necessary and sufficient to ascertain a family for study. Depending on the comprehensiveness of the sampling frame, there may be more than one proband per family. The first proband in a family is sometimes termed the propositus or index case. Additional nonproband-affected relatives are termed secondary cases (Morton, 1982). Careful delineation of probands and nonprobands in families is extremely important in correcting for ascertainment biases in the statistical genetic analysis of inheritance patterns (see, e.g., Greenberg, 1986; Vieland and Hodge, 1995). The Bennett et al. (1995a) definition implies that there would be only one "proband" per family, which could seriously bias analysis of family structures recorded following the recommendations. Marazita (1995) argued that the definition of "proband" used by Bennett et al. (1995a) and other clinicians (e.g., Thompson, et al., 1991) is more properly the definition of "index case," and that "proband" be reserved for the above more general definition of an affected person who is ascer-
52
Letters to the Editor
t a i n e d for study via a p a r t i c u l a r s a m p l i n g s c h e m e . I n B e n n e t t et aL (1995c), t h e a u t h o r s a g r e e d with M a r a z i t a (1995) a n d s t a t e d ( p a r a g r a p h 2, p. 983): ...we would like to amend our definition of "proband" in figure i, example 7a, to read "an affected individual coming to medical attention independent of other family members."
REFERENCES
Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan CK, Resta RG, Lochner-Doyle D, Markel DS, Vincent V, Hamanishi J (1995a) Recommendations for standardized human pedigree nomenclature. Am J Hum Genet 56:745-752. Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan CK, Resta RG, Lochner-Doyle D, Markel DS, Vincent V, Hamanishi J (1995b) Recommendations for standardized human pedigree nomenclature (reprint). J Genet Counsel, 4(in press). Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan CK, Resta RG, Lochner-Doyle D, Markel DS, Vincent V, Hamanishi J (1995c) Reply to Marazita and Curtis. Am J Hum Genet 57:983-984. Greenberg DA (1986) "laaeeffect of proband designation on segregation analysis. Am J Hum Genet 39:329-339. Marazita ML (1995) Defining "proband." Am J Hum Genet 57:981-982. Morton NE (1959) Genetic tests under incomplete ascertainment. Am J Hum Genet 11:1-16. Morton NE (1982) Outline of Genetic Epidemiology. New York: Karger, pp 47-48. Vieland VJ, Hodge SE (1995) Inherent intractability of the ascertainment problem for pedigree data: A general likelihood framework. Am J Hum Genet 56:33-43. Weinberg W (1927) Mathematische grundlagen der Probandenmethode. Z Induktive Abstammungs Vererbungslehre 48:179-228.
Mary L. Marazita, Ph.D. Cleft Palate-Craniofacial Center, 317 Salk Hall, 3501 Terrace St. Department of Oral and Maxillofaciat Surgery Department of Human Genetics University of Pittsburgh Pittsburgh, PA 15261
Letters to the Editor
Audrey Heimler Huntington Disease Program Depamnent of Psychiatry University of Connecticut Health Center Farmington, Connecticut
Changing the Definition of "Proband" in the New Standardized Nomenclature for Pedigrees To the Editor:
Bennett et aL (1995a) presented recommendations of the Pedigree Standardization Task Force of the National Society of Genetic Counselors. Because the article was recently reprinted in this journal (Bennett et al., Vot. 4, No. 4, 1995b), I would like to bring to attention a recent exchange of letters regarding the Bennett et al. (1995a,b) definition of "proband." Bennett et al. (1995a, Fig. 1, p. 746), define "proband" as the "first affected family member coming to medical attention." Marazita (1995) took issue with this definition and Bennett et aL (1995c) agreed. This definition illustrates the dichotomy in the use of the term "proband" by clinicians vs. researchers. Bennett et aL's (1995a) definition is the meaning that clinicians seem to have evolved (see, e.g., Thompson, et aL, 1991). Researchers, on the other hand, rely on the original use of the word "proband" (Weinberg, 1927; Morton, 1959) as an affected person who is necessary and sufficient to ascertain a family for study. Depending on the comprehensiveness of the sampling frame, there may be more than one proband per family. The first proband in a family is sometimes termed the propositus or index case. Additional nonproband-affected relatives are termed secondary cases (Morton, 1982). Careful delineation of probands and nonprobands in families is extremely important in correcting for ascertainment biases in the statistical genetic analysis of inheritance patterns (see, e.g., Greenberg, 1986; Vieland and Hodge, 1995). The Bennett et al. (1995a) definition implies that there would be only one "proband" per family, which could seriously bias analysis of family structures recorded following the recommendations. Marazita (1995) argued that the definition of "proband" used by Bennett et al. (1995a) and other clinicians (e.g., Thompson, et al., 1991) is more properly the definition of "index case," and that "proband" be reserved for the above more general definition of an affected person who is ascer-
52
Letters to the Editor
t a i n e d for study via a p a r t i c u l a r s a m p l i n g s c h e m e . I n B e n n e t t et aL (1995c), t h e a u t h o r s a g r e e d with M a r a z i t a (1995) a n d s t a t e d ( p a r a g r a p h 2, p. 983): ...we would like to amend our definition of "proband" in figure i, example 7a, to read "an affected individual coming to medical attention independent of other family members."
REFERENCES
Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan CK, Resta RG, Lochner-Doyle D, Markel DS, Vincent V, Hamanishi J (1995a) Recommendations for standardized human pedigree nomenclature. Am J Hum Genet 56:745-752. Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan CK, Resta RG, Lochner-Doyle D, Markel DS, Vincent V, Hamanishi J (1995b) Recommendations for standardized human pedigree nomenclature (reprint). J Genet Counsel, 4(in press). Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan CK, Resta RG, Lochner-Doyle D, Markel DS, Vincent V, Hamanishi J (1995c) Reply to Marazita and Curtis. Am J Hum Genet 57:983-984. Greenberg DA (1986) "laaeeffect of proband designation on segregation analysis. Am J Hum Genet 39:329-339. Marazita ML (1995) Defining "proband." Am J Hum Genet 57:981-982. Morton NE (1959) Genetic tests under incomplete ascertainment. Am J Hum Genet 11:1-16. Morton NE (1982) Outline of Genetic Epidemiology. New York: Karger, pp 47-48. Vieland VJ, Hodge SE (1995) Inherent intractability of the ascertainment problem for pedigree data: A general likelihood framework. Am J Hum Genet 56:33-43. Weinberg W (1927) Mathematische grundlagen der Probandenmethode. Z Induktive Abstammungs Vererbungslehre 48:179-228.
Mary L. Marazita, Ph.D. Cleft Palate-Craniofacial Center, 317 Salk Hall, 3501 Terrace St. Department of Oral and Maxillofaciat Surgery Department of Human Genetics University of Pittsburgh Pittsburgh, PA 15261
