4. de Groote-Ceuterick C. Het electronenmicroscopischonderzoek van huidbiopten als bijdrage in de diagnostiek van metabole aandoeningen van het zenuwstelsel. PhD thesis, Born-Bunge Foundatioduniversitaire Instelling Antwerpen, 1988- 1989
markers included family members with abnormal EEG traits and family members with other forms of epilepsy 151. There seems little doubt that JME is an inherited disease, but this analysis does not establish an autosomal recessive mode of inheritance for it.
Is Juvenile Myoclonic
“Departmentof Psychiatry Mount Sinai Medical Center
Epilepsy an Autosomal Recessive Disease? David A. Greenberg, PhD,* Martina Durner, MD,* Antonio V. Delgado-Escueta, MD,? and Dieter Janz, MD$ Panayiotopoulos and Obeid [l] have collected a rare set of families with juvenile myoclonic epilepsy UME). This data set has the potential to be very useful in elucidating the genetics of JME. However, their analysis claiming to establish autosomal recessive inheritance for JME contains a number of methodological problems, some of which are discussed below. First, simple segregation analysis was used for the analysis. The authors do not give details of the segregation analysis, but “simple segregation analysis” usually implies nuclear families, no inbreeding, and Hardy-Weinberg equilibrium. These conditions are apparently not met. Second, there is no indication how the pedigrees were ascertained or how ascertainment bias correction was carried out. Failure to correct the ascertainment bias or ascertaining with a nonrigorous protocol can lead to totally spurious results 12, 31. Third, in attempting to correct for age of onset, all ma$ jicted siblings younger than 14 years were eliminated from the analysis, but only about one-half of aflected siblings were eliminated. As a result, the segregation ratio for this age group was 1.0-only affected people were included, biasing the results upward. A proper age-of-onset correction would include the age-dependent probability of being affected. Fourth, the segregation ratio is said to be between 0.12 and 0.18, the latter figure incorporating the
markers included family members with abnormal EEG traits and family members with other forms of epilepsy 151. There seems little doubt that JME is an inherited disease, but this analysis does not establish an autosomal recessive mode of inheritance for it.
Is Juvenile Myoclonic
“Departmentof Psychiatry Mount Sinai Medical Center
Epilepsy an Autosomal Recessive Disease? David A. Greenberg, PhD,* Martina Durner, MD,* Antonio V. Delgado-Escueta, MD,? and Dieter Janz, MD$ Panayiotopoulos and Obeid [l] have collected a rare set of families with juvenile myoclonic epilepsy UME). This data set has the potential to be very useful in elucidating the genetics of JME. However, their analysis claiming to establish autosomal recessive inheritance for JME contains a number of methodological problems, some of which are discussed below. First, simple segregation analysis was used for the analysis. The authors do not give details of the segregation analysis, but “simple segregation analysis” usually implies nuclear families, no inbreeding, and Hardy-Weinberg equilibrium. These conditions are apparently not met. Second, there is no indication how the pedigrees were ascertained or how ascertainment bias correction was carried out. Failure to correct the ascertainment bias or ascertaining with a nonrigorous protocol can lead to totally spurious results 12, 31. Third, in attempting to correct for age of onset, all ma$ jicted siblings younger than 14 years were eliminated from the analysis, but only about one-half of aflected siblings were eliminated. As a result, the segregation ratio for this age group was 1.0-only affected people were included, biasing the results upward. A proper age-of-onset correction would include the age-dependent probability of being affected. Fourth, the segregation ratio is said to be between 0.12 and 0.18, the latter figure incorporating the
