Browsing by Author "Kansu, T."
Now showing 1 - 8 of 8
Results Per Page
Sort Options
Item Open Access Assessment of the visual pathways in patients with neurofibromatosis-1 by 3S-space technique with 3-Tesla MRI(TÜBİTAK, 2019-12) Saraç, Ö.; Algın, Oktay; Beyazal, M.; Anlar, B.; Varan, A.; Kansu, T.Background/aim: We aimed to evaluate the size/tortuosity of the optic nerve (ON) and the dilatation of the ON sheath (ONS) in neurofibromatosis type 1 (NF-1) patients with 3T-MRI, and to assess the usefulness of 3D-SPACE in imaging the optic pathway, ON, and ONS in NF-1 patients. Materials and methods: Twenty consecutive NF-1 patients without optic pathway glioma (OPG) (Group 1), 16 consecutive NF-1 patients with OPG (Group 2), and 19 controls were included in this study. The thickness and tortuosity of the ON and the diameter of the ONS were measured on STIR and 3D-SPACE images. Results: The thickness of the ON was similar in all groups on STIR images (P>0.05). The mean ONS diameter was higher in Group 2 with this sequence (P=0.009). Controls had significantly lower grades of ON tortuosity than Groups 1 and 2 (P=0.001), and Group 1 had significantly lower ON tortuosity compared to Group 2 (P=0.001). Severe tortuosity was only detected in Group 2. Conclusion: ON tortuosity and ONS diameter were increased in NF-1 patients in the presence of OPG. High-resolution cranium imaging with the 3D-SPACE technique using 3T-MRI seems to be helpful for detection of the optic pathway morphology and pathologies in NF-1 patients.Item Open Access Cortical connectivity in the face of congenital structural changes—A case of homozygous LAMC3 mutation(John Wiley & Sons Ltd., 2021-08) Demirayak, P.; Oğuz, Kader Karlı; Üstün, Fatma Seyhun; Ürgen, Buse Merve; Topaç, Yasemin; Gilani, İrtiza; Kansu, T.; Saygı, S.; Özçelik, Tayfun; Boyacı, Hüseyin; Doerschner, KatjaThe homozygous LAMC3 gene mutation is associated with severe bilateral smoothening and thickening of the lateral occipital cortex . Despite this and further significant changes in gray matter structure, a patient harboring this mutation exhibited a range of remarkably intact perceptual abilities . One possible explanation of this perceptual sparing could be that the white matter structural integrity and functional connectivity in relevant pathways remained intact. To test this idea, we used diffusion tensor and functional magnetic resonance imaging to investigate functional connectivity in resting-state networks in major structural pathways involved in object perception and visual attention and corresponding microstructural integrity in a patient with homozygous LAMC3 mutation and sex, age, education, and socioeconomically matched healthy control group. White matter microstructural integrity results indicated widespread disruptions in both intra- and interhemispheric structural connections except inferior longitudinal fasciculus. With a few exceptions, the functional connectivity between the patient's adjacent gray matter regions of major white matter tracts of interest was conserved. In addition, functional localizers for face, object, and place areas showed similar results with a representative control, providing an explanation for the patient's intact face, place, and object recognition abilities. To generalize this finding, we also compared functional connectivity between early visual areas and face, place, and object category-selective areas, and we found that the functional connectivity of the patient was not different from the control group. Overall, our results provided complementary information about the effects of LAMC3 gene mutation on the human brain including intact temporo-occipital structural and functional connectivity that are compatible with preserved perceptual abilities.Item Open Access Homozygosity mapping and targeted genomic sequencing reveal the game responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred(Cold Spring Harbor Laboratory Press, 2011) Gulsuner, Süleyman; Tekinay, Ayşe Begüm; Doerschner, Katja; Boyaci, Hüseyin; Bilguvar, K.; Ünal, Hilal; Örs, Aslıhan; Onat, O. Emre; Atalar, Ergin; Basak, A. N.; Topaloglu, H.; Kansu, T.; Tan, M.; Tan, U.; Gunel, M.; Özçelik, TayfunThe biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1-13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans.Item Open Access Homozygous LAMC3 mutation links to structural and functional changes in visual attention networks(Elsevier, 2019) Ürgen, Buse M.; Topaç, Yasemin; Üstün, F. Seyhun; Demirayak, Pınar; Oğuz, Kader K.; Kansu, T.; Saygı, S.; Özçelik, Tayfun; Boyacı, Hüseyin; Doerschner, KatjaThe occipital lobe contains a substantial part of the neural machinery involved in visual perception. Mutations in the LAMC3 gene have recently been shown to cause complex bilateral occipital cortical gyration abnormalities. However, to what extent these structural changes impact visual behavior is not known. We recorded responses for two screening test batteries targeting visual function (Leuven - Perceptual Organization Screening Test, Cortical Vision Screening Test) and measured eye fixation performance in a visual attention experiment from a patient with homozygous LAMC3 gene mutation. Using voxel-based morphometry (VBM) we quantitatively assessed the extent of structural changes brought on by the genetic mutation by comparing mean cortical curvature, cortical thickness, and gray matter volume in 34 cortical areas between patient and an age-, sex-, and education-matched control group. Anatomical connectivity between these cortical areas was investigated by a structural covariance analysis. Visual screening-, and behavioral results revealed that the patient's impairments were predominantly in visuo-spatial attention. Consistent with this, VBM and structural connectivity results revealed significant structural changes in cortical regions subserving attentional functions. We conclude that the LAMC3 gene mutation affects cortical areas beyond the occipital lobe and primarily those visual functions that involve heavily distributed networks - such as visuo-spatial attention.Item Open Access Mitochondrial serine protease HTRA2 p.G3999S in a kindred with essential tremor and Parkinson disease(National Academy of Sciences, 2014) Gülümser, Hilal Ünal; Gulsuner, S.; Mercan, F. N.; Onat, Onur Emre; Walsh, T.; Shahin, H.; Lee, M. K.; Dogu, O.; Kansu, T.; Topaloglu, H.; Elibol, B.; Akbostanci, C.; King, M. C.; Özçelik, Tayfun; Tekinay, Ayşe B.Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.Item Open Access Neuro-ophthalmologic findings in humans with quadrupedal locomotion(2012) Sarac O.; Gulsuner, S.; Yildiz-Tasci, Y.; Ozcelik, T.; Kansu, T.Purpose: To report the neuro-ophthalmologic findings in four patients from the same family with cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ)2 associated with quadrupedal locomotion. Method: A case series. Results: All four patients carry the private missense mutation, WDR81 p.P856L. The brain Magnetic Resonance Imaging (MRI) of these patients revealed morphological abnormalities including mild hypoplasia of the corpus callosum, and atrophy of superior, middle, and inferior peduncles of the cerebellum. All patients had down-beat nystagmus, while two male patients additionally had bilateral temporal disc pallor along with ring-shaped macular atrophy. Conclusions: The neuro-ophthalmic examination in CAMRQ2 revealed downbeat nystagmus in all patients, and temporal disc pallor and macular atrophy in two patients. It remains to be determined whether these findings are consistent in other forms of CAMRQ with mutations in VLDLR or CA8. © 2012 Informa Healthcare USA, Inc.Item Open Access Reply to tzoulis et al.: genetic and clinical heterogeneity of essential tremor(National Academy of Sciences, 2015) Gülsuner, Hilal Ünal; Gülsuner, S.; Mercan, F.; Onat, Onur Emre; Walsh, T.; Shahin, H.; Lee, M.; Dogu, O.; Kansu, T.; Topaloglu, H.; Elibol, B.; Akbostanci, C.; King, M. -C.; Özçelik, Tayfun; Tekinay, Ayse B.In addressing our recent report of HTRA2 p.G399S as the gene and mutation responsible for essential tremor and subsequent Parkinson disease in a large kindred (1), Tzoulis et al. (2) screened this mutation in patients with Parkinson disease, essential tremor, tremulous cervical dystonia, and nontremulous cervical dystonia patients, and did not find a significant difference in carrier frequency compared with the general population. Their observation replicates our experience, in that in the kindred of our study, HTRA2 p.G399S was responsible for essential tremor and, among homozygotes, for Parkinson disease, but as we reported, this allele was not responsible for essential tremor in other families from the same population. Both these observations support the conclusion that essential tremor is a heterogeneous disease, both clinically and genetically (3). In addition to HTRA2, two other genes for essential tremor have been identified: DNAJC13 and FUS, and still other responsible genes have been mapped to chromosomes 2p22-24, 3q13, and 6p23 (1, 4). In any one patient, mutation at only one of these genes is sufficient for development of essential tremor, but the responsible gene differs among patients. These two features—the severity of individual causal mutations and different responsible genes in different families—are characteristic of genetic heterogeneity of complex diseases generally (5). Phenotypic features of a genetically heterogeneous disease may offer clues as to the responsible gene. In the family harboring mutation in HTRA2, Parkinson disease appeared after more than a decade of essential tremor. Also, cervical dystonia was not among the presenting signs in any of the family members. These clinical features differ from the series of patients screened by Tzoulis et al. Some of the patients screened by Tzoulis et al. may harbor HTRA2 mutations other than p.G399S that would be revealed by more complete sequencing; this would be interesting to learn. It is also possible that mutations in the other known genes for essential tremor may be present in these patients. If not, then these patients, like those from the other kindreds in our series, offer the opportunity to identify additional causal genes for essential tremor.Item Open Access Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene(BMJ Group, 2008) Kaplan, Y.; Vargel, I.; Kansu, T.; Akin, B.; Rohmann, E.; Kamaci, S.; Uz, E.; Ozcelik, T.; Wollnik, B.; Akarsu, N. A.Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. Results: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c.686C>G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family. Conclusions: A novel p.R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females.