2011 From Van Aalst Cohen to Van der Graaf: a question

Is the failure to find an FH mutation due to the fact that scientists have not yet discovered all mutations? This much-used argument in industry-funded papers today begs a very important question. The failure to even bring up the neglected question of misdiagnosis is telling. Dr. Van Aalst Cohen provided strong evidence that the presence of the FCH in FH scoring results is probable, but could not eliminate the underlying question: do we know the majority of mutations accounting for FH? Five years later, with more mutations having been discovered and greater technology at her disposal, Dr. Anouk Van der Graaf tackled precisely this same issue, but with a clever strategy: focusing on children precludes a greater part of the non-FH and the FCH. FH tends to reveal high LDLC from the outset of life, whereas acquired LDLC disorders and FCH as well tend to reveal high LDLC much later in life. By restricting her study to children Van der Graaf precludes a large number of non-FH and the FCH from the scoring system results at the outset. Using an “unequivocal” diagnosis of FH, but after precluding a majority of the Non-FH and FCH, how many “large effect” mutations are as yet unaccounted for?

2011 From Van Aalst Cohen to Van der Graaf: a question about FH diagnosis