Figure 1.

Identification of SLC52A2 mutation in family A despite initial false linkage. (a) Pedigree showing allele segregation of flanking markers on chromosome 8 in family A. Alleles are indicated by PCR fragment size (in base pair) and correspond to markers that are underlined on the genetic map of chromosome 8 (right). Markers in the pter–qter ordering are shown from top to bottom. Genetic distance (in cM) between markers is indicated. The marker that was not part of the initial study¹⁰ is highlighted in yellow. SLC52A2 localization in qter is indicated by a red mark. Note that the affected uncle (V.5) is homozygous neither for the marker closest to SLC52A2 tested in the initial study¹⁰ nor with the closest marker tested in this study, indicating the presence of a possibly ancient recombination located very close to SLC52A2. (b) Sanger sequencing of the mutation c.916G>A causing the p.(Gly306Arg) (G306R): the two patients are homozygous for the substitution. The parents of patient VI.1 are heterozygous for the same substitution and their healthy children are either heterozygous (individual VI.2) or wild type (individual VI.4).