J Korean Med Sci.  2008 Dec;23(6):959-963. 10.3346/jkms.2008.23.6.959.

Clinical and Genetic Analysis of Korean Patients with Facioscapulohumeral Muscular Dystrophy

Affiliations
  • 1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 2Department of Neurology, Seoul National University College of Medicine, Seoul, Korea. pks1126@chol.com

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominantly inherited muscular disorder, which is characterized by weakness of facial, shoulder and hip girdle, humeral, and anterior distal leg muscles. The FSHD gene has been mapped to 4q35 and a deletion of integral copies of a 3.3-kb DNA repeat motif named D4Z4 was known to be the genetic background of the disorder. Although FSHD is the second most common muscular dystrophy in adulthood, there were few reports on the genetically confirmed patients in Korea. Recently, we experienced four Korean patients with clinical features resembling FSHD. In order to confirm the diagnosis, conventional Southern blot (SB) analysis by using double digestion with EcoRI and BlnI and hybridization with p13E-11 probe was performed in three patients and newly developed long polymerase chain reaction (PCR) method was used for one patient because genomic DNA was not enough for conventional SB for this patient. All patients were demonstrated to have shortened D4Z4 repeats that were consistent with FSHD. Therefore, we could confirm the diagnosis of FSHD in four Korean patients and appropriate genetic counseling was done for the patients and their families. It is of note that long-PCR method could be a good alternative for conventional SB when D4Z4 repeats were less than 5.

Keyword

Facioscapulohumeral Muscular Dystrophy; FSHD; D4Z4; Korean

MeSH Terms

Adolescent
Adult
Blotting, Southern
Chromosomes, Human, Pair 4
Female
Genotype
Humans
Korea
Male
Muscular Dystrophy, Facioscapulohumeral/*diagnosis/genetics
Pedigree
Phenotype
*Sequence Deletion
Tandem Repeat Sequences

Figure

  • Fig. 1 Pedigrees of 4 patients with FSHD. Circle, female; square, male; black symbol, affected with shortened D4Z4 repeats; gray symbol, possibly affected by history; arrow, proband; N, tested for D4Z4 repeats and found normal.

  • Fig. 2 Representative results of Southern blot analysis. Convential electrophoresis and Southern blot analysis of EcoRI (E) and EcoRI/BlnI (E/B) digested DNA from patient 4 and his father revealed a 28-kb sized EcoRI fragment (*) resistant to BlnI digestion only in patient 4. Another EcoRI framgenet between 38 kb and 48 kb disappeared after BlnI digestion (#). M1, 1-kb size marker; M2, high molecular weight size marker.

  • Fig. 3 Result of long-PCR amplification in patient 2. A 18.4 kb PCR product (*) corresponding to 3 D4Z4 repeats was detected in patient 2 (lane 1) while a 11.8 kb sized band (#) was noticed in positive control (P) with 2 D4Z4 repeats. No band was observed in the patient's brother (lane 2) and in negative control (N). M, high molecular weight size marker.


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