Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy.
Congenital ataxia with cerebellar hypoplasia is a heterogeneous group of disorders that presents with motor disability, hypotonia, incoordination, and impaired motor development. Among these, disequilibrium syndrome describes a constellation of findings including non-progressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia following an autosomal recessive pattern of inheritance and can be caused by mutations in the Very Low Density Lipoprotein Receptor (VLDLR). Interestingly, while the majority of patients with VLDL-associated cerebellar hypoplasia in the literature use bipedal gait, the previously reported patients of Turkish decent have demonstrated similar neurological sequelae, but rely on quadrupedal gait. We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia.
Kolb
Luis E
LE
Department of Neurosurgery, Neurobiology, Program on Neurogenetics Yale University School of Medicine, New Haven, CT, USA.
Arlier
Zulfikar
Z
Yalcinkaya
Cengiz
C
Ozturk
Ali K
AK
Moliterno
Jennifer A
JA
Erturk
Ozdem
O
Bayrakli
Fatih
F
Korkmaz
Baris
B
DiLuna
Michael L
ML
Yasuno
Katsuhito
K
Bilguvar
Kaya
K
Ozcelik
Tayfun
T
Tuysuz
Beyhan
B
State
Matthew W
MW
Gunel
Murat
M
D002524:Cerebellar Ataxia / Q000235:genetics; D002648:Child; D003241:Consanguinity; D020234:Gait Ataxia / Q000235:genetics; D006720:Homozygote; D006801:Humans; D054082:Lissencephaly / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009849:Olivopontocerebellar Atrophies / Q000175:diagnosis / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*; D017384:Sequence Deletion; D035781:Siblings; D014421:Turkey
D011973:Receptors, LDL; C036053:VLDL receptor