X-linked infantile spinal muscular atrophy: clinical definition and molecular mapping.
OBJECTIVE
X-linked infantile spinal-muscular atrophy (XL-SMA) is a rare disorder, which presents with the clinical characteristics of hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have previously reported a single family with XL-SMA that mapped to Xp11.3-q11.2. Here we report further clinical description of XL-SMA plus an additional seven unrelated (XL-SMA) families from North America and Europe that show linkage data consistent with the same region.


METHODS
We first investigated linkage to the candidate disease gene region using microsatellite repeat markers. We further saturated the candidate disease gene region using polymorphic microsatellite repeat markers and single nucleotide polymorphisms in an effort to narrow the critical region. Two-point and multipoint linkage analysis was performed using the Allegro software package.


RESULTS
Linkage analysis of all XL-SMA families displayed linkage consistent with the original XL-SMA region.


CONCLUSIONS
The addition of new families and new markers has narrowed the disease gene interval for a XL-SMA locus between SNP FLJ22843 near marker DXS 8080 and SNP ARHGEF9 which is near DXS7132 (Xp11.3-Xq11.1).
Dressman
Devin
D
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
Ahearn
Mary Ellen
ME
Yariz
Kemal O
KO
Basterrecha
Hugo
H
Martínez
Francisco
F
Palau
Francesc
F
Barmada
M Michael
MM
Clark
Robin Dawn
RD
Meindl
Alfons
A
Wirth
Brunhilde
B
Hoffman
Eric P
EP
Baumbach-Reardon
Lisa
L
D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D004247:DNA / Q000235:genetics; D005190:Family; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*
D004247:DNA