Hereditary macular degeneration (HMD) in 246 cases traced to one gene-source in central Sweden

Abstract

Two large families with hereditary macular degeneration (HMD), one from central Sweden (116 cases), the other from northern Sweden (130 cases), were found to have a common origin. The disease was traced to a couple born in central Sweden (county of Kopparberg) in the 17th century. The disease was introduced to northern Sweden (county of Västerbotten) in the 18th century. Age of onset and severity of the disease varied widely in the 246 patients, 130 men and 116 women, carrying the same mutated gene. The distribution of age of onset was bimodal with one maximum before and one maximum after puberty. Women more often than men had their onset before puberty. The disease was inherited as an autosomal dominant trait with a high but not complete penetrance. At least one patient appeared to be homozygous.

Molecular Physiology of Bestrophins: Multifunctional Membrane Proteins Linked to Best Disease and Other Retinopathies

“…For example, pigment accumulation was found before 1 yr of age in one child, whereas another child had completely normal vision and retinal structure at the age of 24. Although the variable expressivity of macular lesions is common, affected individuals are usually reliably identified by abnormal EOGs (150,151). Thus it seems clear that the disease occurs in two steps, with the initial lesion being associated with a depressed EOG and a second step (or series of steps) leading to the vitelliform lesion.…”

“…More than 250 cases were traced back to a single gene source in the 17th century (150). The locus for BVMD was determined by linkage analysis to be located in a pericentric region on chromosome 11, at 11q13, near the markers D11S956, FCER1B, and UGB (56,194).…”

Bestrophin 1 – Phenotypes and Functional Aspects in Bestrophinopathies

“…1 It took until the 1970s before the first attempts were made to identify the gene underlying the disease in a Swedish family. 2 The locus for VMD was determined by linkage analysis to localize in the pericentric region of chromosome 11 (11q13). 3,4 In 1998 the human BEST1 gene was cloned.…”

A V235L Mutation of the Human BEST1 Gene Associated with Best Macular Dystrophy with Intra-familial Clinical Variations

“…Best disease is the second most common form of juvenile macular degeneration, with a bimodal onset with two peaks, one around 3-9 years and in the twenties [2], but there is a great variability in onset from infants to over 50 years of age. This disorder is characterized by variable deposition of yellowish pigments (lipofuscin) in the sub retinal space.…”