Genetic identity of Marinesco-Sjögren/myoglobinuria and CCFDN syndromes.
OBJECTIVE
To describe three Gypsy families with Marinesco-Sjögren syndrome (MSS), demyelinating neuropathy, and recurrent episodes of myoglobinuria in five of the six affected subjects. Because these families originated from the same genetically isolated founder population as did patients with congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome, and because the two syndromes have clinical manifestations in common, we hypothesized that the two related, albeit distinct, syndromes may represent clinical variants of a single genetic disorder.


METHODS
Clinical studies were conducted and linkage and haplotype analyses were performed for the three families. A total of 16 individuals, including the 6 with MSS and 10 unaffected relatives, were genotyped for six polymorphic microsatellite markers from the CCFDN region on 18qter.


RESULTS
Linkage analysis of markers in the 18qter region, where we previously had located the CCFDN gene, produced a lod score of 3.55, demonstrating colocalization of the gene responsible for MSS with demyelinating neuropathy and myoglobinuria with the CCFDN gene. Moreover, the patients with MSS shared the conserved marker haplotype found in CCFDN chromosomes.


CONCLUSIONS
These data suggest that Marinesco-Sjögren syndrome with peripheral neuropathy and myoglobinuria, and congenital cataracts facial dysmorphism neuropathy syndrome are genetically identical and are caused by a single founder mutation.
Merlini
L
L
Neuromuscular Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
Gooding
R
R
Lochmüller
H
H
Müller-Felber
W
W
Walter
M C
MC
Angelicheva
D
D
Talim
B
B
Hallmayer
J
J
Kalaydjieva
L
L
D000293:Adolescent; D002386:Cataract / Q000151:congenital* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002887:Chromosomes, Human, Pair 18; D005145:Face / Q000002:abnormalities*; D005260:Female; D018703:Founder Effect; D005858:Germany; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007558:Italy; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009212:Myoglobinuria / Q000235:genetics* / Q000503:physiopathology; D009422:Nervous System Diseases / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D006178:Romani People / Q000235:genetics*; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000503:physiopathology; D013577:Syndrome