Infantile bilateral striatal necrosis maps to chromosome 19q.
BACKGROUND
Infantile bilateral striatal necrosis (IBSN) encompasses several syndromes of bilateral symmetric degeneration of the caudate nucleus, putamen, and globus pallidus. Autosomal recessive IBSN is characterized clinically by developmental arrest beginning at age 7 to 15 months, dysphagia, choreoathetosis, pendular nystagmus and optic atrophy, and severe progressive atrophy of the basal ganglia on MRI.


OBJECTIVE
To map the gene causing IBSN.


METHODS
A 10-cM genome-wide linkage scan was initially performed on five affected and five unaffected individuals. The extended family was included in the analysis to narrow the candidate region. Logarithm of odds (LOD) score was calculated using the SUPERLINK program.


RESULTS
Linkage to the chromosomal region 19q13.32-13.41 was established (Z(max) = 6.27 at theta = 0.02 at locus D19S412). Recombination events and a common disease-bearing haplotype defined a critical region of 1.2 Mb between the loci D19S596 proximally and D19S867 distally.


CONCLUSIONS
IBSN maps to the chromosomal region 19q13.32-13.41. The presence of a common haplotype in all the patients suggests that the disease is caused by a single mutation derived from a single ancestral founder in all the families.
Basel-Vanagaite
L
L
Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, 49100, Israel. basel@post.tau.ac.il
Straussberg
R
R
Ovadia
H
H
Kaplan
A
A
Magal
N
N
Shorer
Z
Z
Shalev
H
H
Walsh
C
C
Shohat
M
M
D017668:Age of Onset; D018912:Arabs / Q000208:ethnology; D002421:Caudate Nucleus / Q000473:pathology; D002648:Child; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D003241:Consanguinity; D003342:Corpus Striatum / Q000473:pathology*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005917:Globus Pallidus / Q000473:pathology; D006239:Haplotypes; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007557:Israel; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009336:Necrosis; D010375:Pedigree; D011699:Putamen / Q000473:pathology; D011995:Recombination, Genetic; D013577:Syndrome