Microcephaly-thin corpus callosum syndrome maps to 8q23.2-q24.12.
Postnatal microcephaly is defined as normal head circumference at birth, which progressively declines to more than 2 standard deviations below the average for the patient's age and sex. We describe four patients from three consanguineous families of Arab Bedouin origin who presented with autosomal recessive inheritance of progressive microcephaly, spasticity, thin corpus callosum, pyramidal signs, and intellectual disability. Homozygosity mapping (Human Mapping NspI 250K arrays, Affymetrix, Santa Clara, CA) placed the disease locus at 8q23.2-q24.12. The candidate region includes 22 known or predicted genes, including RAD21, which is related to the cohesion complex EIF3H, which is involved in translation initiation, and TAF2, which may be involved in intellectual disability. Identification of the causative gene in our reported family will shed light on the pathogenesis of this severe condition.
Department of Pediatric Neurology and Child Development, Schneider Children's Medical Center of Israel, Petah Tikva, Israel. brosh3826@bezeqint.net
Ayelet
A
Halevy
Lina
L
Basel-Vanagaite
Avinoam
A
Shuper
Shlomit
S
Helman
Adi
A
Har-Zahav
Efrat
E
Birk
Idit
I
Maya
Liora
L
Kornreich
Dov
D
Inbar
Gudrun
G
Nürnberg
Peter
P
Nürnberg
Tamar
T
Steinberg
Rachel
R
Straussberg
D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping / Q000379:methods; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003337:Corpus Callosum / Q000473:pathology*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D013577:Syndrome