An unusual family with Leber's hereditary optic neuropathy and facioscapulohumeral muscular dystrophy

Abstract

We performed an observational prospective analysis to study the clinical characteristics as well as a molecular genetic analysis of 17 members of a Thai family who had visual loss and/or muscle weakness. Their blood mitochondrial DNA were examined for the presence of the G11778A Leber's hereditary optic neuropathy (LHON) mutation. Facioscapulohumeral muscular dystrophy (FSHD) DNA analysis was performed in four members who had visual loss. Of 17 family members, the eight members who had the 11778 LHON mutation were all from branch 'a'. Three of these eight members had FSHD with a 17-27-kb deletion of a tandem repeat in the 4q35 subtelomere, and two had been clinically diagnosed as FSHD. Four of six examined members in branch 'b' showed muscular dystrophy clinically diagnosed as FSHD. No correlation of blood DNA analysis between LHON and FSHD in affected members was found. We describe the first family with FSHD and G11778A LHON in which a mutation in mitochondrial DNA at nucleotide position 11778 of branch 'a' was found to be the origin of the mutation.

Transmission of heteroplasmic G11778A in extensive pedigrees of Thai Leber hereditary optic neuropathy

“…2). When the average degree of heteroplasmy was compared with those of the next generations (generations 3 and 4), it was found to be significantly higher (P=0.005; ANOVA) in F19, the heteroplasmic family previously reported in Chuenkongkaew et al (2005). The mean percentages of heteroplasmy of each generation between three generations (generations 2, 3 and 4) of F09 (P=0.103) and F24 (P=0.245) had a pattern similar to that of F19 (Fig.…”

“…If heteroplasmy does actually reflect a recent mutational event (Savontaus 1995), the recent high incidence of the G11778A mutation in Thailand presents an intriguing problem. In two of the pedigrees in our collection the G11778A mutation appeared to have been recently developed in each family: one family has been described by Chuenkongkaew et al (2005) (F19) and the other was F09 (Fig. 1a) presented in this study.…”

Facioscapulohumeral Muscular Dystrophy: More Complex than it Appears

“…In these patients the D4Z4 reduced allele is associated with a well-known pathogenic mutation of other genes, causing complex and overlapping phenotypes as summarized in Table 2 . In particular, patients with mitochondrial myopathy/ FSHD [ 121 ], Becker dystrophy/FSHD [ 122 ], Duchenne dystrophy/FSHD [ 123 , 124 ], Leber’s hereditary optic neuropathy/FSHD [ 125 ], LGMD1C with rippling disease/FSHD [ 126 ], myotonic dystrophy type 1/FSHD [ 127 ] were reported suggesting the possibility of a synergistic effect of those simultaneous mutations in reaching and in modulating the clinical expression.…”

The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees

“…One family (F19) was found to have two genetic diseases simultaneously: LHON, a mitochondrial disease and facioscapulohumeral dystrophy (FSHD), an autosomal dominant disorder (Chuenkongkaew et al 2005). …”