Ancestral Origin of the First Indian Families with Myotonic Dystrophy Type 2

Background: Myotonic dystrophy type 2 (DM2) is caused by a CCTG repeat expansion in intron 1 of the CCHC-Type Zinc Finger Nucleic Acid Binding Protein (CNBP) gene. Previous studies indicated that this repeat expansion originates from separate founders.Objective: This study was set out to determine whether or not patients with DM2 originating from European and non-European countries carry the previously described European founder haplotypes.Methods: Haplotype analysis was performed in 59 DM2 patients from 29 unrelated families. Twenty-three families were from European descent and 6 families originated from non-European countries (India, Suriname and Morocco). Seven short tandem repeats (CL3N122, CL3N99, CL3N59, CL3N117, CL3N119, CL3N19 and CL3N23) and 4 single nucleotide polymorphisms (SNP) (rs1871922, rs1384313, rs4303883 and CGAP_886192) in and around the CNBPgene were used to construct patients’ haplotypes. These haplotypes were compared to the known DM2 haplotypes to determine the ancestral origin of the CNBPrepeat expansion.Results: Of 41 patients, the haplotype could be assigned to the previously described Caucasian haplotypes. Three patients from Morocco and Portugal had a haplotype identical to the earlier reported Moroccan haplotype. Twelve patients from India and Suriname, however, carried a haplotype that seems distinct from the previously reported haplotypes. Three individuals could not be assigned to a specific haplotype.Conclusion: The ancestral origin of DM2 in India might be distinct from the Caucasian families and the solely described Japanese patient. However, we were unable to establish this firmly due to the limited genetic variation in the region surrounding the CNBPgene.