title: A novel autosomal recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p12.
abstract: 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.
authors.affiliation: Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Hospital, POB 12000, Jerusalem 91120, Israel. alos@hadassah.org.il
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
authors.forename: Lekbir
authors.initials: L
authors.lastname: Baala
authors.forename: Dov
authors.initials: D
authors.lastname: Soffer
authors.forename: Lea
authors.initials: L
authors.lastname: Averbuch-Heller
authors.forename: Shlomo
authors.initials: S
authors.lastname: Dotan
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: J Moshe
authors.initials: JM
authors.lastname: Gomori
authors.forename: Adnan
authors.initials: A
authors.lastname: Genem
authors.forename: Meir
authors.initials: M
authors.lastname: Neufeld
authors.forename: Oded
authors.initials: O
authors.lastname: Abramsky
authors.forename: Joel
authors.initials: J
authors.lastname: Zlotogora
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000150:complications / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009886:Ophthalmoplegia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D014792:Visual Acuity / Q000502:physiology