Brain Advance Access originally published online on November 17, 2004
Brain 2005 128(1):42-51; doi:10.1093/brain/awh338
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Brain Vol. 128 No. 1 © Guarantors of Brain 2004; all rights reserved
A novel autosomal recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p12
1 Department of Neurology, the Agnes Ginges Center for Human Neurogenetics, and Departments of 2 Pathology 3 Ophthalmology and 4 Radiology, Hadassah-Hebrew University Hospital, Jerusalem, 5 Department of Neurology, Rabin Medical Center, Petah-Tikva, 6 Clalit Health Services, Jerusalem and 7 Department of Community Genetics, Public Health Services, Ministry of Health, Jerusalem Israel, 8 Department of Genetics, INSERM U-393, Hopital Necker-Enfants Malades, Paris, France and 9 Department of Medical Genetics, INH, Rabat, Morocco
Correspondence to: Dr A. Lossos, Department of Neurology, Hadassah University Hospital, POB 12000, Jerusalem 91120, Israel E-mail: alos{at}hadassah.org.il
We describe a new autosomal recessive myopathy of early onset and very slow progression distinguished by the prominent external ophthalmoplegia in 16 subjects of eight families from a large and highly inbred Arab community. Characteristic clinical features include mild facial and skeletal muscle weakness and atrophy more pronounced proximally in the upper limbs, facial dysmorphism and scoliosis associated with conjugate, non-restrictive ocular motility impairment greatest in the upgaze and without ptosis or aberrant eye movements. Orbital MRI in the patients demonstrated atrophy with fatty replacement of the oculorotatory muscles. The major pathological alteration on skeletal muscle biopsy was a marked type 1 fibre predominance with core-like formations. A genome wide search for regions of homozygosity in the affected members from two informative families identified linkage with chromosome 17p13.1-p12 markers. Maximum two-point logarithm of odds scores were obtained at loci D17S1803 and AFMA070WD1 (Zmax = 3.74 at 
= 0). Two independent recombination events at D17S1812 and D17S947 further defined a critical region of 12 cM. Several genes map to this interval, including a cluster of sarcomeric myosin heavy chain genes. One of these genes, MYH2, is involved in inclusion body myopathy 3, but no exonic mutations were found by direct sequencing. The molecular basis for this new myopathy remains to be identified.
# Deceased
This work is dedicated to the memory of our dear colleague and friend, the late Dr Lea Averbuch-Heller. Her enthusiasm and wisdom made this work possible.