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39 results on '"Tarailo-Graovac M"'

1. metPropagate: network-guided propagation of metabolomic information for prioritization of metabolic disease genes

Author

Graham Linck, Emma J., Richmond, Phillip A., Tarailo-Graovac, M., Engelke, U.F.H., Kluijtmans, L.A.J., Coene, K.L.M., Wevers, R.A., Karnebeek, C.D. van, Mostafavi, S., Graham Linck, Emma J., Richmond, Phillip A., Tarailo-Graovac, M., Engelke, U.F.H., Kluijtmans, L.A.J., Coene, K.L.M., Wevers, R.A., Karnebeek, C.D. van, and Mostafavi, S.

Abstract

Contains fulltext : 220744.pdf (publisher's version ) (Open Access)

Published
2020

2. metPropagate: network-guided propagation of metabolomic information for prioritization of metabolic disease genes

Author

Graham Linck, Emma J., Richmond, Phillip A., Tarailo-Graovac, M., Engelke, U.F.H., Kluijtmans, L.A.J., Coene, K.L.M., Wevers, R.A., Karnebeek, C.D. van, Mostafavi, S., Graham Linck, Emma J., Richmond, Phillip A., Tarailo-Graovac, M., Engelke, U.F.H., Kluijtmans, L.A.J., Coene, K.L.M., Wevers, R.A., Karnebeek, C.D. van, and Mostafavi, S.

Abstract

Contains fulltext : 220744.pdf (publisher's version ) (Open Access)

Published
2020

3. metPropagate: network-guided propagation of metabolomic information for prioritization of metabolic disease genes

Author

Graham Linck, Emma J., Richmond, Phillip A., Tarailo-Graovac, M., Engelke, U.F.H., Kluijtmans, L.A.J., Coene, K.L.M., Wevers, R.A., Karnebeek, C.D. van, Mostafavi, S., Graham Linck, Emma J., Richmond, Phillip A., Tarailo-Graovac, M., Engelke, U.F.H., Kluijtmans, L.A.J., Coene, K.L.M., Wevers, R.A., Karnebeek, C.D. van, and Mostafavi, S.

Abstract

Contains fulltext : 220744.pdf (publisher's version ) (Open Access)

Published
2020

4. PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights

Author

Johnstone, D.L., Al-Shekaili, H.H., Tarailo-Graovac, M., Wolf, N.I., Ivy, A.S., Demarest, S., Roussel, Y., Ciapaite, J., Roermund, C.W.T. van, Kernohan, K.D., Kosuta, C., Ban, K., Ito, Y., McBride, S., Al-Thihli, K., Abdelrahim, R.A., Koul, R., Futaisi, A. Al, Haaxma, C.A., Olson, H., Sigurdardottir, L.Y., Arnold, G.L., Gerkes, E.H., Boon, M., Heiner-Fokkema, M.R., Noble, S., Bosma, M., Jans, J., Koolen, D.A., Kamsteeg, E.J., Drogemoller, B., Ross, C.J., Majewski, J., Cho, M.T., Begtrup, A., Wasserman, W.W., Bui, T., Brimble, E., Violante, S., Houten, S.M., Wevers, R.A., Faassen, M. van, Kema, I.P., Lepage, N., Lines, M.A., Dyment, D.A., Wanders, R.J., Verhoeven-Duif, N., Ekker, M., Boycott, K.M., Friedman, J.M., Pena, I.A., Karnebeek, C.D. van, Johnstone, D.L., Al-Shekaili, H.H., Tarailo-Graovac, M., Wolf, N.I., Ivy, A.S., Demarest, S., Roussel, Y., Ciapaite, J., Roermund, C.W.T. van, Kernohan, K.D., Kosuta, C., Ban, K., Ito, Y., McBride, S., Al-Thihli, K., Abdelrahim, R.A., Koul, R., Futaisi, A. Al, Haaxma, C.A., Olson, H., Sigurdardottir, L.Y., Arnold, G.L., Gerkes, E.H., Boon, M., Heiner-Fokkema, M.R., Noble, S., Bosma, M., Jans, J., Koolen, D.A., Kamsteeg, E.J., Drogemoller, B., Ross, C.J., Majewski, J., Cho, M.T., Begtrup, A., Wasserman, W.W., Bui, T., Brimble, E., Violante, S., Houten, S.M., Wevers, R.A., Faassen, M. van, Kema, I.P., Lepage, N., Lines, M.A., Dyment, D.A., Wanders, R.J., Verhoeven-Duif, N., Ekker, M., Boycott, K.M., Friedman, J.M., Pena, I.A., and Karnebeek, C.D. van

Abstract

Contains fulltext : 202680.pdf (publisher's version ) (Closed access), Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug disc

Published
2019

5. Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy

Author

Karnebeek, C.D. van, Ramos, R.J., Wen, X.Y., Tarailo-Graovac, M., Gleeson, Joseph G., Skrypnyk, C., Kluijtmans, L.A.J., Willemsen, M.A.A.P., Rodenburg, R.J., Huigen, M., Zaki, Maha S., Wevers, R.A., Karnebeek, C.D. van, Ramos, R.J., Wen, X.Y., Tarailo-Graovac, M., Gleeson, Joseph G., Skrypnyk, C., Kluijtmans, L.A.J., Willemsen, M.A.A.P., Rodenburg, R.J., Huigen, M., Zaki, Maha S., and Wevers, R.A.

Abstract

Contains fulltext : 207864.pdf (publisher's version ) (Open Access)

Published
2019

6. PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights

Author

Johnstone, D.L., Al-Shekaili, H.H., Tarailo-Graovac, M., Wolf, N.I., Ivy, A.S., Demarest, S., Roussel, Y., Ciapaite, J., Roermund, C.W.T. van, Kernohan, K.D., Kosuta, C., Ban, K., Ito, Y., McBride, S., Al-Thihli, K., Abdelrahim, R.A., Koul, R., Futaisi, A. Al, Haaxma, C.A., Olson, H., Sigurdardottir, L.Y., Arnold, G.L., Gerkes, E.H., Boon, M., Heiner-Fokkema, M.R., Noble, S., Bosma, M., Jans, J., Koolen, D.A., Kamsteeg, E.J., Drogemoller, B., Ross, C.J., Majewski, J., Cho, M.T., Begtrup, A., Wasserman, W.W., Bui, T., Brimble, E., Violante, S., Houten, S.M., Wevers, R.A., Faassen, M. van, Kema, I.P., Lepage, N., Lines, M.A., Dyment, D.A., Wanders, R.J., Verhoeven-Duif, N., Ekker, M., Boycott, K.M., Friedman, J.M., Pena, I.A., Karnebeek, C.D. van, Johnstone, D.L., Al-Shekaili, H.H., Tarailo-Graovac, M., Wolf, N.I., Ivy, A.S., Demarest, S., Roussel, Y., Ciapaite, J., Roermund, C.W.T. van, Kernohan, K.D., Kosuta, C., Ban, K., Ito, Y., McBride, S., Al-Thihli, K., Abdelrahim, R.A., Koul, R., Futaisi, A. Al, Haaxma, C.A., Olson, H., Sigurdardottir, L.Y., Arnold, G.L., Gerkes, E.H., Boon, M., Heiner-Fokkema, M.R., Noble, S., Bosma, M., Jans, J., Koolen, D.A., Kamsteeg, E.J., Drogemoller, B., Ross, C.J., Majewski, J., Cho, M.T., Begtrup, A., Wasserman, W.W., Bui, T., Brimble, E., Violante, S., Houten, S.M., Wevers, R.A., Faassen, M. van, Kema, I.P., Lepage, N., Lines, M.A., Dyment, D.A., Wanders, R.J., Verhoeven-Duif, N., Ekker, M., Boycott, K.M., Friedman, J.M., Pena, I.A., and Karnebeek, C.D. van

Abstract

Contains fulltext : 202680.pdf (publisher's version ) (Closed access), Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug disc

Published
2019

7. Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy

Author

Karnebeek, C.D. van, Ramos, R.J., Wen, X.Y., Tarailo-Graovac, M., Gleeson, Joseph G., Skrypnyk, C., Kluijtmans, L.A.J., Willemsen, M.A.A.P., Rodenburg, R.J., Huigen, M., Zaki, Maha S., Wevers, R.A., Karnebeek, C.D. van, Ramos, R.J., Wen, X.Y., Tarailo-Graovac, M., Gleeson, Joseph G., Skrypnyk, C., Kluijtmans, L.A.J., Willemsen, M.A.A.P., Rodenburg, R.J., Huigen, M., Zaki, Maha S., and Wevers, R.A.

Abstract

Contains fulltext : 207864.pdf (publisher's version ) (Open Access)

Published
2019

8. PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights

Author

Johnstone, D.L., Al-Shekaili, H.H., Tarailo-Graovac, M., Wolf, N.I., Ivy, A.S., Demarest, S., Roussel, Y., Ciapaite, J., Roermund, C.W.T. van, Kernohan, K.D., Kosuta, C., Ban, K., Ito, Y., McBride, S., Al-Thihli, K., Abdelrahim, R.A., Koul, R., Futaisi, A. Al, Haaxma, C.A., Olson, H., Sigurdardottir, L.Y., Arnold, G.L., Gerkes, E.H., Boon, M., Heiner-Fokkema, M.R., Noble, S., Bosma, M., Jans, J., Koolen, D.A., Kamsteeg, E.J., Drogemoller, B., Ross, C.J., Majewski, J., Cho, M.T., Begtrup, A., Wasserman, W.W., Bui, T., Brimble, E., Violante, S., Houten, S.M., Wevers, R.A., Faassen, M. van, Kema, I.P., Lepage, N., Lines, M.A., Dyment, D.A., Wanders, R.J., Verhoeven-Duif, N., Ekker, M., Boycott, K.M., Friedman, J.M., Pena, I.A., Karnebeek, C.D. van, Johnstone, D.L., Al-Shekaili, H.H., Tarailo-Graovac, M., Wolf, N.I., Ivy, A.S., Demarest, S., Roussel, Y., Ciapaite, J., Roermund, C.W.T. van, Kernohan, K.D., Kosuta, C., Ban, K., Ito, Y., McBride, S., Al-Thihli, K., Abdelrahim, R.A., Koul, R., Futaisi, A. Al, Haaxma, C.A., Olson, H., Sigurdardottir, L.Y., Arnold, G.L., Gerkes, E.H., Boon, M., Heiner-Fokkema, M.R., Noble, S., Bosma, M., Jans, J., Koolen, D.A., Kamsteeg, E.J., Drogemoller, B., Ross, C.J., Majewski, J., Cho, M.T., Begtrup, A., Wasserman, W.W., Bui, T., Brimble, E., Violante, S., Houten, S.M., Wevers, R.A., Faassen, M. van, Kema, I.P., Lepage, N., Lines, M.A., Dyment, D.A., Wanders, R.J., Verhoeven-Duif, N., Ekker, M., Boycott, K.M., Friedman, J.M., Pena, I.A., and Karnebeek, C.D. van

Abstract

Contains fulltext : 202680.pdf (publisher's version ) (Closed access), Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug disc

Published
2019

9. Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy

Author

Karnebeek, C.D. van, Ramos, R.J., Wen, X.Y., Tarailo-Graovac, M., Gleeson, Joseph G., Skrypnyk, C., Kluijtmans, L.A.J., Willemsen, M.A.A.P., Rodenburg, R.J., Huigen, M., Zaki, Maha S., Wevers, R.A., Karnebeek, C.D. van, Ramos, R.J., Wen, X.Y., Tarailo-Graovac, M., Gleeson, Joseph G., Skrypnyk, C., Kluijtmans, L.A.J., Willemsen, M.A.A.P., Rodenburg, R.J., Huigen, M., Zaki, Maha S., and Wevers, R.A.

Abstract

Contains fulltext : 207864.pdf (publisher's version ) (Open Access)

Published
2019

10. The role of the clinician in the multi-omics era: are you ready?

Author

Karnebeek, C.D. van, Wortmann, S.B., Tarailo-Graovac, M., Langeveld, M., Ferreira, C., Kamp, Jiddeke M. van de, Wevers, R.A., Wanders, R.J., Boycott, K.M., Karnebeek, C.D. van, Wortmann, S.B., Tarailo-Graovac, M., Langeveld, M., Ferreira, C., Kamp, Jiddeke M. van de, Wevers, R.A., Wanders, R.J., and Boycott, K.M.

Abstract

Contains fulltext : 191976.pdf (publisher's version ) (Open Access)

Published
2018

11. Sialic acid catabolism by N-acetylneuraminate pyruvate lyase is essential for muscle function

Author

Wen, X.Y., Tarailo-Graovac, M., Brand-Arzamendi, K., Willems, A.P., Rakic, B., Huijben, K., Scherpenzeel, M. van, Engelke, U.F.H., Wevers, R.A., Karnebeek, C.D. van, Lefeber, D.J., Wen, X.Y., Tarailo-Graovac, M., Brand-Arzamendi, K., Willems, A.P., Rakic, B., Huijben, K., Scherpenzeel, M. van, Engelke, U.F.H., Wevers, R.A., Karnebeek, C.D. van, and Lefeber, D.J.

Abstract

Contains fulltext : 200388.pdf (publisher's version ) (Open Access)

Published
2018

12. Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review

Author

Graham, E., Lee, J., Price, M., Tarailo-Graovac, M., Matthews, A., Engelke, U.F., Tang, J., Kluijtmans, L.A.J., Wevers, R.A., Wasserman, W.W., Karnebeek, C.D. van, Mostafavi, S., Graham, E., Lee, J., Price, M., Tarailo-Graovac, M., Matthews, A., Engelke, U.F., Tang, J., Kluijtmans, L.A.J., Wevers, R.A., Wasserman, W.W., Karnebeek, C.D. van, and Mostafavi, S.

Abstract

Contains fulltext : 200196.pdf (publisher's version ) (Open Access)

Published
2018

13. The genotypic and phenotypic spectrum of MTO1 deficiency

Author

O'Byrne, J.J., Tarailo-Graovac, M., Ghani, Aisha, Champion, M.P., Deshpande, Charu, Dursun, Ali, Kluijtmans, L.A.J., Smeitink, J., Wevers, R.A., Engelke, U.F.H., Rodenburg, R.J.T., Salvarinova, R., Karnebeek, C.D. van, O'Byrne, J.J., Tarailo-Graovac, M., Ghani, Aisha, Champion, M.P., Deshpande, Charu, Dursun, Ali, Kluijtmans, L.A.J., Smeitink, J., Wevers, R.A., Engelke, U.F.H., Rodenburg, R.J.T., Salvarinova, R., and Karnebeek, C.D. van

Abstract

Contains fulltext : 184066.pdf (publisher's version ) (Open Access)

Published
2018

14. SimPEL: Simulation-based power estimation for sequencing studies of low-prevalence conditions

Author

Mak, L, Li, M, Cao, C, Gordon, P, Tarailo-Graovac, M, Bousman, C, Wang, P, Long, Q, Mak, L, Li, M, Cao, C, Gordon, P, Tarailo-Graovac, M, Bousman, C, Wang, P, and Long, Q

Abstract

Power estimations are important for optimizing genotype-phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill-suited for the inherent challenges of studies for low-prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challenges include small sample sizes and the need to leverage genetic annotation resources in association analyses for the purpose of ranking potential causal genes. We present SimPEL, a simulation-based program providing power estimations for the design of low-prevalence condition studies. SimPEL integrates the usage of gene annotation resources for association analyses. Customizable parameters, including the penetrance of the putative causal allele and the employed pathogenic scoring system, allow SimPEL to realistically model a large range of study designs. To demonstrate the effects of various parameters on power, we estimated the power of several simulated designs using SimPEL and captured power trends in agreement with observations from current literature on low-frequency condition studies. SimPEL, as a tool, provides researchers studying low-frequency conditions with an intuitive and highly flexible avenue for statistical power estimation. The platform-independent "batteries included" executable and default input files are available at https://github.com/precisionomics/SimPEL.

Published
2018

15. The role of the clinician in the multi-omics era: are you ready?

Author

Karnebeek, C.D. van, Wortmann, S.B., Tarailo-Graovac, M., Langeveld, M., Ferreira, C., Kamp, Jiddeke M. van de, Wevers, R.A., Wanders, R.J., Boycott, K.M., Karnebeek, C.D. van, Wortmann, S.B., Tarailo-Graovac, M., Langeveld, M., Ferreira, C., Kamp, Jiddeke M. van de, Wevers, R.A., Wanders, R.J., and Boycott, K.M.

Abstract

Contains fulltext : 191976.pdf (publisher's version ) (Open Access)

Published
2018

16. Sialic acid catabolism by N-acetylneuraminate pyruvate lyase is essential for muscle function

Author

Wen, X.Y., Tarailo-Graovac, M., Brand-Arzamendi, K., Willems, A.P., Rakic, B., Huijben, K., Scherpenzeel, M. van, Engelke, U.F.H., Wevers, R.A., Karnebeek, C.D. van, Lefeber, D.J., Wen, X.Y., Tarailo-Graovac, M., Brand-Arzamendi, K., Willems, A.P., Rakic, B., Huijben, K., Scherpenzeel, M. van, Engelke, U.F.H., Wevers, R.A., Karnebeek, C.D. van, and Lefeber, D.J.

Abstract

Contains fulltext : 200388.pdf (publisher's version ) (Open Access)

Published
2018

17. Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review

Author

Graham, E., Lee, J., Price, M., Tarailo-Graovac, M., Matthews, A., Engelke, U.F., Tang, J., Kluijtmans, L.A.J., Wevers, R.A., Wasserman, W.W., Karnebeek, C.D. van, Mostafavi, S., Graham, E., Lee, J., Price, M., Tarailo-Graovac, M., Matthews, A., Engelke, U.F., Tang, J., Kluijtmans, L.A.J., Wevers, R.A., Wasserman, W.W., Karnebeek, C.D. van, and Mostafavi, S.

Abstract

Contains fulltext : 200196.pdf (publisher's version ) (Open Access)

Published
2018

18. The genotypic and phenotypic spectrum of MTO1 deficiency

Author

O'Byrne, J.J., Tarailo-Graovac, M., Ghani, Aisha, Champion, M.P., Deshpande, Charu, Dursun, Ali, Kluijtmans, L.A.J., Smeitink, J., Wevers, R.A., Engelke, U.F.H., Rodenburg, R.J.T., Salvarinova, R., Karnebeek, C.D. van, O'Byrne, J.J., Tarailo-Graovac, M., Ghani, Aisha, Champion, M.P., Deshpande, Charu, Dursun, Ali, Kluijtmans, L.A.J., Smeitink, J., Wevers, R.A., Engelke, U.F.H., Rodenburg, R.J.T., Salvarinova, R., and Karnebeek, C.D. van

Abstract

Contains fulltext : 184066.pdf (publisher's version ) (Open Access)

Published
2018

19. Sialic acid catabolism by N-acetylneuraminate pyruvate lyase is essential for muscle function

Author

Wen, X.Y., Tarailo-Graovac, M., Brand-Arzamendi, K., Willems, A.P., Rakic, B., Huijben, K., Scherpenzeel, M. van, Engelke, U.F.H., Wevers, R.A., Karnebeek, C.D. van, Lefeber, D.J., Wen, X.Y., Tarailo-Graovac, M., Brand-Arzamendi, K., Willems, A.P., Rakic, B., Huijben, K., Scherpenzeel, M. van, Engelke, U.F.H., Wevers, R.A., Karnebeek, C.D. van, and Lefeber, D.J.

Abstract

Contains fulltext : 200388.pdf (publisher's version ) (Open Access)

Published
2018

20. Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review

Author

Graham, E., Lee, J., Price, M., Tarailo-Graovac, M., Matthews, A., Engelke, U.F., Tang, J., Kluijtmans, L.A.J., Wevers, R.A., Wasserman, W.W., Karnebeek, C.D. van, Mostafavi, S., Graham, E., Lee, J., Price, M., Tarailo-Graovac, M., Matthews, A., Engelke, U.F., Tang, J., Kluijtmans, L.A.J., Wevers, R.A., Wasserman, W.W., Karnebeek, C.D. van, and Mostafavi, S.

Abstract

Contains fulltext : 200196.pdf (publisher's version ) (Open Access)

Published
2018

21. The genotypic and phenotypic spectrum of MTO1 deficiency

Author

O'Byrne, J.J., Tarailo-Graovac, M., Ghani, Aisha, Champion, M.P., Deshpande, Charu, Dursun, Ali, Kluijtmans, L.A.J., Smeitink, J., Wevers, R.A., Engelke, U.F.H., Rodenburg, R.J.T., Salvarinova, R., Karnebeek, C.D. van, O'Byrne, J.J., Tarailo-Graovac, M., Ghani, Aisha, Champion, M.P., Deshpande, Charu, Dursun, Ali, Kluijtmans, L.A.J., Smeitink, J., Wevers, R.A., Engelke, U.F.H., Rodenburg, R.J.T., Salvarinova, R., and Karnebeek, C.D. van

Abstract

Contains fulltext : 184066.pdf (publisher's version ) (Open Access)

Published
2018

22. The role of the clinician in the multi-omics era: are you ready?

Author

Karnebeek, C.D. van, Wortmann, S.B., Tarailo-Graovac, M., Langeveld, M., Ferreira, C., Kamp, Jiddeke M. van de, Wevers, R.A., Wanders, R.J., Boycott, K.M., Karnebeek, C.D. van, Wortmann, S.B., Tarailo-Graovac, M., Langeveld, M., Ferreira, C., Kamp, Jiddeke M. van de, Wevers, R.A., Wanders, R.J., and Boycott, K.M.

Abstract

Contains fulltext : 191976.pdf (publisher's version ) (Open Access)

Published
2018

23. Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD).

Author

Balasubramaniam, Shanti, Balasubramaniam, Shanti, Lewis, B, Mock, DM, Said, HM, Tarailo-Graovac, M, Mattman, A, van Karnebeek, CD, Thorburn, DR, Rodenburg, RJ, Christodoulou, J, Balasubramaniam, Shanti, Balasubramaniam, Shanti, Lewis, B, Mock, DM, Said, HM, Tarailo-Graovac, M, Mattman, A, van Karnebeek, CD, Thorburn, DR, Rodenburg, RJ, and Christodoulou, J

Abstract

Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated

Published
2017

24. Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD).

Author

Balasubramaniam, Shanti, Balasubramaniam, Shanti, Lewis, B, Mock, DM, Said, HM, Tarailo-Graovac, M, Mattman, A, van Karnebeek, CD, Thorburn, DR, Rodenburg, RJ, Christodoulou, J, Balasubramaniam, Shanti, Balasubramaniam, Shanti, Lewis, B, Mock, DM, Said, HM, Tarailo-Graovac, M, Mattman, A, van Karnebeek, CD, Thorburn, DR, Rodenburg, RJ, and Christodoulou, J

Abstract

Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated

Published
2017

25. Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

Author

Balasubramaniam, S., Lewis, B., Mock, D.M., Said, H.M., Tarailo-Graovac, M., Mattman, A., Karnebeek, C.D. van, Thorburn, D.R., Rodenburg, R.J.T., Christodoulou, J., Balasubramaniam, S., Lewis, B., Mock, D.M., Said, H.M., Tarailo-Graovac, M., Mattman, A., Karnebeek, C.D. van, Thorburn, D.R., Rodenburg, R.J.T., and Christodoulou, J.

Abstract

Item does not contain fulltext, Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated with hypo

Published
2017

26. NANS-mediated synthesis of sialic acid is required for brain and skeletal development

Author

Karnebeek, C.D. van, Bonafe, L., Wen, X.Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A.M., Garavelli, L., Mammi, I., Donnai, D., Cormier, V., Heron, D., Nishimura, G., Uchikawa, S., Campos-Xavier, B., Rossi, A., Hennet, T., Brand-Arzamendi, K., Rozmus, J., Harshman, K., Girardi, E., Superti-Furga, G., Dewan, T., Collingridge, A., Halparin, J., Ross, C.J., Allen, M.I. van, Rossi, A, Engelke, U.F.H., Kluijtmans, L.A., Heeft, E. van der, Renkema, H., Brouwer, A.P. de, Huijben, K., Zijlstra, F.S., Heisse, T., Boltje, T.J., Wasserman, W.W., Rivolta, C., Unger, S., Lefeber, D.J., Wevers, R.A., Superti-Furga, A., Karnebeek, C.D. van, Bonafe, L., Wen, X.Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A.M., Garavelli, L., Mammi, I., Donnai, D., Cormier, V., Heron, D., Nishimura, G., Uchikawa, S., Campos-Xavier, B., Rossi, A., Hennet, T., Brand-Arzamendi, K., Rozmus, J., Harshman, K., Girardi, E., Superti-Furga, G., Dewan, T., Collingridge, A., Halparin, J., Ross, C.J., Allen, M.I. van, Rossi, A, Engelke, U.F.H., Kluijtmans, L.A., Heeft, E. van der, Renkema, H., Brouwer, A.P. de, Huijben, K., Zijlstra, F.S., Heisse, T., Boltje, T.J., Wasserman, W.W., Rivolta, C., Unger, S., Lefeber, D.J., Wevers, R.A., and Superti-Furga, A.

Abstract

Item does not contain fulltext

Published
2017

27. Identification of a large intronic transposal insertion in SLC17A5 causing sialic acid storage disease

Author

Tarailo-Graovac, M. (Maja), Drögemöller, B.I. (Britt I.), Wasserman, W.W. (Wyeth W.), Ross, C.J., Ouweland, A.M.W. (Ans) van den, Darin, N. (Niklas), Kollberg, G. (Gittan), Van Karnebeek, C.D.M. (Clara D. M.), Blomqvist, M. (Maria), Tarailo-Graovac, M. (Maja), Drögemöller, B.I. (Britt I.), Wasserman, W.W. (Wyeth W.), Ross, C.J., Ouweland, A.M.W. (Ans) van den, Darin, N. (Niklas), Kollberg, G. (Gittan), Van Karnebeek, C.D.M. (Clara D. M.), and Blomqvist, M. (Maria)

Abstract

Background: Sialic acid storage diseases are neurodegenerative disorders characterized by accumulation of sialic acid in the lysosome. These disorders are caused by mutations in SLC17A5, the gene encoding sialin, a sialic acid transporter located in the lysosomal membrane. The most common form of sialic acid storage disease is the slowly progressive Salla disease, presenting with hypotonia, ataxia, epilepsy, nystagmus and findings of cerebral and cerebellar atrophy. Hypomyelination and corpus callosum hypoplasia are typical as well. We report a 16 year-old boy with an atypically mild clinical phenotype of sialic acid storage disease characterized by psychomotor retardation and a mixture of spasticity and rigidity but no ataxia, and only weak features of hypomyelination and thinning of corpus callosum on MRI of the brain. Results: The thiobarbituric acid method showed elevated levels of free sialic acid in urine and fibroblasts, indicating sialic acid storage disease. Initial Sanger sequencing of SLC17A5 coding regions did not show any pathogenic variants, although exon 9 could not be sequenced. Whole exome sequencing followed by RNA and genomic DNA analysis identified a homozygous 6040 bp insertion in intron 9 of SLC17A5 corresponding to a long interspersed element-1 retrotransposon (KF425758.1). This insertion adds two splice sites, both resulting in a frameshift which in turn creates a premature stop codon 4 bp into intron 9. Conclusions: This study describes a novel pathogenic variant in SLC17A5, namely an intronic transposal insertion, in a patient with mild biochemical and clinical phenotypes. The presence of a small fraction of normal transcript may explain the mild phenotype. This case illustrates the importance of including lysosomal sialic acid storage disease in the differential diagnosis of developmental delay with postnatal onset and hypomyelination, as well as intronic regions in the genetic investigation of inborn errors of metabolism.

Published
2017
Full Text
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28. Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD).

Author

Balasubramaniam, Shanti, Balasubramaniam, Shanti, Lewis, B, Mock, DM, Said, HM, Tarailo-Graovac, M, Mattman, A, van Karnebeek, CD, Thorburn, DR, Rodenburg, RJ, Christodoulou, J, Balasubramaniam, Shanti, Balasubramaniam, Shanti, Lewis, B, Mock, DM, Said, HM, Tarailo-Graovac, M, Mattman, A, van Karnebeek, CD, Thorburn, DR, Rodenburg, RJ, and Christodoulou, J

Abstract

Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated

Published
2017

29. Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

Author

Balasubramaniam, S., Lewis, B., Mock, D.M., Said, H.M., Tarailo-Graovac, M., Mattman, A., Karnebeek, C.D. van, Thorburn, D.R., Rodenburg, R.J.T., Christodoulou, J., Balasubramaniam, S., Lewis, B., Mock, D.M., Said, H.M., Tarailo-Graovac, M., Mattman, A., Karnebeek, C.D. van, Thorburn, D.R., Rodenburg, R.J.T., and Christodoulou, J.

Abstract

Item does not contain fulltext, Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated with hypo

Published
2017

30. NANS-mediated synthesis of sialic acid is required for brain and skeletal development

Author

Karnebeek, C.D. van, Bonafe, L., Wen, X.Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A.M., Garavelli, L., Mammi, I., Turolla, L., Breen, C., Donnai, D., Cormier, V., Heron, D., Nishimura, G., Uchikawa, S., Campos-Xavier, B., Rossi, A., Hennet, T., Brand-Arzamendi, K., Rozmus, J., Harshman, K., Stevenson, B.J., Girardi, E., Superti-Furga, G., Dewan, T., Collingridge, A., Halparin, J., Ross, C.J., Allen, M.I. van, Rossi, A, Engelke, U.F.H., Kluijtmans, L.A., Heeft, E. van der, Renkema, H., Brouwer, A.P.M. de, Huijben, K., Zijlstra, F.S., Heisse, T., Boltje, T.J., Wasserman, W.W., Rivolta, C., Unger, S., Lefeber, D.J., Wevers, R.A., Superti-Furga, A., Karnebeek, C.D. van, Bonafe, L., Wen, X.Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A.M., Garavelli, L., Mammi, I., Turolla, L., Breen, C., Donnai, D., Cormier, V., Heron, D., Nishimura, G., Uchikawa, S., Campos-Xavier, B., Rossi, A., Hennet, T., Brand-Arzamendi, K., Rozmus, J., Harshman, K., Stevenson, B.J., Girardi, E., Superti-Furga, G., Dewan, T., Collingridge, A., Halparin, J., Ross, C.J., Allen, M.I. van, Rossi, A, Engelke, U.F.H., Kluijtmans, L.A., Heeft, E. van der, Renkema, H., Brouwer, A.P.M. de, Huijben, K., Zijlstra, F.S., Heisse, T., Boltje, T.J., Wasserman, W.W., Rivolta, C., Unger, S., Lefeber, D.J., Wevers, R.A., and Superti-Furga, A.

Abstract

Item does not contain fulltext

Published
2017

31. NANS-mediated synthesis of sialic acid is required for brain and skeletal development

Author

Karnebeek, C.D. van, Bonafe, L., Wen, X.Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A.M., Garavelli, L., Mammi, I., Turolla, L., Breen, C., Donnai, D., Cormier, V., Heron, D., Nishimura, G., Uchikawa, S., Campos-Xavier, B., Rossi, A., Hennet, T., Brand-Arzamendi, K., Rozmus, J., Harshman, K., Stevenson, B.J., Girardi, E., Superti-Furga, G., Dewan, T., Collingridge, A., Halparin, J., Ross, C.J., Allen, M.I. van, Rossi, A, Engelke, U.F.H., Kluijtmans, L.A., Heeft, E. van der, Renkema, H., Brouwer, A.P.M. de, Huijben, K., Zijlstra, F.S., Heisse, T., Boltje, T.J., Wasserman, W.W., Rivolta, C., Unger, S., Lefeber, D.J., Wevers, R.A., Superti-Furga, A., Karnebeek, C.D. van, Bonafe, L., Wen, X.Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A.M., Garavelli, L., Mammi, I., Turolla, L., Breen, C., Donnai, D., Cormier, V., Heron, D., Nishimura, G., Uchikawa, S., Campos-Xavier, B., Rossi, A., Hennet, T., Brand-Arzamendi, K., Rozmus, J., Harshman, K., Stevenson, B.J., Girardi, E., Superti-Furga, G., Dewan, T., Collingridge, A., Halparin, J., Ross, C.J., Allen, M.I. van, Rossi, A, Engelke, U.F.H., Kluijtmans, L.A., Heeft, E. van der, Renkema, H., Brouwer, A.P.M. de, Huijben, K., Zijlstra, F.S., Heisse, T., Boltje, T.J., Wasserman, W.W., Rivolta, C., Unger, S., Lefeber, D.J., Wevers, R.A., and Superti-Furga, A.

Abstract

Item does not contain fulltext

Published
2017

33. Exome Sequencing and the Management of Neurometabolic Disorders

Author

Tarailo-Graovac, M., Shyr, C., Ross, C.J., Horvath, G.A., Salvarinova, R., Ye, X.C., Zhang, L.H., Bhavsar, A.P., Lee, J.J., Drögemöller, B.I., Abdelsayed, M., Alfadhel, M., Armstrong, L., Baumgartner, M.R., Burda, P., Connolly, M.B., Cameron, J., Demos, M., Dewan, T., Dionne, J., Evans, A.M., Friedman, J.M., Garber, I., Lewis, S., Ling, J., Mandal, R., Mattman, A., McKinnon, M., Michoulas, A., Metzger, D., Ogunbayo, O.A., Rakic, B., Rozmus, J., Ruben, P., Sayson, B., Santra, S., Schultz, K.R., Selby, K., Shekel, P., Sirrs, S., Skrypnyk, C., Superti-Furga, A., Turvey, S.E., Allen, M.I. van, Wishart, D., Wu, J., Zafeiriou, D., Kluijtmans, L.A.J., Wevers, R.A., Eydoux, P., Lehman, A.M., Vallance, H., Stockler-Ipsiroglu, S., Sinclair, G., Wasserman, W.W., Karnebeek, C.D. van, Tarailo-Graovac, M., Shyr, C., Ross, C.J., Horvath, G.A., Salvarinova, R., Ye, X.C., Zhang, L.H., Bhavsar, A.P., Lee, J.J., Drögemöller, B.I., Abdelsayed, M., Alfadhel, M., Armstrong, L., Baumgartner, M.R., Burda, P., Connolly, M.B., Cameron, J., Demos, M., Dewan, T., Dionne, J., Evans, A.M., Friedman, J.M., Garber, I., Lewis, S., Ling, J., Mandal, R., Mattman, A., McKinnon, M., Michoulas, A., Metzger, D., Ogunbayo, O.A., Rakic, B., Rozmus, J., Ruben, P., Sayson, B., Santra, S., Schultz, K.R., Selby, K., Shekel, P., Sirrs, S., Skrypnyk, C., Superti-Furga, A., Turvey, S.E., Allen, M.I. van, Wishart, D., Wu, J., Zafeiriou, D., Kluijtmans, L.A.J., Wevers, R.A., Eydoux, P., Lehman, A.M., Vallance, H., Stockler-Ipsiroglu, S., Sinclair, G., Wasserman, W.W., and Karnebeek, C.D. van

Abstract

Item does not contain fulltext

Published
2016

34. Clinical delineation of the PACS1-related syndrome--Report on 19 patients

Author

Schuurs-Hoeijmakers, J.H.M., Landsverk, M.L., Foulds, N., Kukolich, M.K., Gavrilova, R.H., Greville-Heygate, S., Hanson-Kahn, A., Bernstein, J.A., Glass, J., Chitayat, D., Burrow, T.A., Husami, A., Collins, K., Wusik, K., Aa, N. van der, Kooy, F., Brown, K.T., Gadzicki, D., Kini, U., Alvarez, S., Fernandez-Jaen, A., McGehee, F., Selby, K., Tarailo-Graovac, M., Allen, M., Karnebeek, C.D. van, Stavropoulos, D.J., Marshall, C.R., Merico, D., Gregor, A., Zweier, C., Hopkin, R.J., Chu, Y.W., Chung, B.H., Vries, B. de, Devriendt, K., Hurles, M.E., Brunner, H.G., Schuurs-Hoeijmakers, J.H.M., Landsverk, M.L., Foulds, N., Kukolich, M.K., Gavrilova, R.H., Greville-Heygate, S., Hanson-Kahn, A., Bernstein, J.A., Glass, J., Chitayat, D., Burrow, T.A., Husami, A., Collins, K., Wusik, K., Aa, N. van der, Kooy, F., Brown, K.T., Gadzicki, D., Kini, U., Alvarez, S., Fernandez-Jaen, A., McGehee, F., Selby, K., Tarailo-Graovac, M., Allen, M., Karnebeek, C.D. van, Stavropoulos, D.J., Marshall, C.R., Merico, D., Gregor, A., Zweier, C., Hopkin, R.J., Chu, Y.W., Chung, B.H., Vries, B. de, Devriendt, K., Hurles, M.E., and Brunner, H.G.

Abstract

Contains fulltext : 167655.pdf (publisher's version ) (Closed access), We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual "wavy" profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases.

Published
2016

35. Exome Sequencing and the Management of Neurometabolic Disorders

Author

Tarailo-Graovac, M., Shyr, C., Ross, C.J., Horvath, G.A., Salvarinova, R., Ye, X.C., Zhang, L.H., Bhavsar, A.P., Lee, J.J., Drögemöller, B.I., Abdelsayed, M., Alfadhel, M., Armstrong, L., Baumgartner, M.R., Burda, P., Connolly, M.B., Cameron, J., Demos, M., Dewan, T., Dionne, J., Evans, A.M., Friedman, J.M., Garber, I., Lewis, S., Ling, J., Mandal, R., Mattman, A., McKinnon, M., Michoulas, A., Metzger, D., Ogunbayo, O.A., Rakic, B., Rozmus, J., Ruben, P., Sayson, B., Santra, S., Schultz, K.R., Selby, K., Shekel, P., Sirrs, S., Skrypnyk, C., Superti-Furga, A., Turvey, S.E., Allen, M.I. van, Wishart, D., Wu, J., Zafeiriou, D., Kluijtmans, L.A.J., Wevers, R.A., Eydoux, P., Lehman, A.M., Vallance, H., Stockler-Ipsiroglu, S., Sinclair, G., Wasserman, W.W., Karnebeek, C.D. van, Tarailo-Graovac, M., Shyr, C., Ross, C.J., Horvath, G.A., Salvarinova, R., Ye, X.C., Zhang, L.H., Bhavsar, A.P., Lee, J.J., Drögemöller, B.I., Abdelsayed, M., Alfadhel, M., Armstrong, L., Baumgartner, M.R., Burda, P., Connolly, M.B., Cameron, J., Demos, M., Dewan, T., Dionne, J., Evans, A.M., Friedman, J.M., Garber, I., Lewis, S., Ling, J., Mandal, R., Mattman, A., McKinnon, M., Michoulas, A., Metzger, D., Ogunbayo, O.A., Rakic, B., Rozmus, J., Ruben, P., Sayson, B., Santra, S., Schultz, K.R., Selby, K., Shekel, P., Sirrs, S., Skrypnyk, C., Superti-Furga, A., Turvey, S.E., Allen, M.I. van, Wishart, D., Wu, J., Zafeiriou, D., Kluijtmans, L.A.J., Wevers, R.A., Eydoux, P., Lehman, A.M., Vallance, H., Stockler-Ipsiroglu, S., Sinclair, G., Wasserman, W.W., and Karnebeek, C.D. van

Abstract

Item does not contain fulltext

Published
2016

36. Clinical delineation of the PACS1-related syndrome--Report on 19 patients

Author

Schuurs-Hoeijmakers, J.H.M., Landsverk, M.L., Foulds, N., Kukolich, M.K., Gavrilova, R.H., Greville-Heygate, S., Hanson-Kahn, A., Bernstein, J.A., Glass, J., Chitayat, D., Burrow, T.A., Husami, A., Collins, K., Wusik, K., Aa, N. van der, Kooy, F., Brown, K.T., Gadzicki, D., Kini, U., Alvarez, S., Fernandez-Jaen, A., McGehee, F., Selby, K., Tarailo-Graovac, M., Allen, M., Karnebeek, C.D. van, Stavropoulos, D.J., Marshall, C.R., Merico, D., Gregor, A., Zweier, C., Hopkin, R.J., Chu, Y.W., Chung, B.H., Vries, B. de, Devriendt, K., Hurles, M.E., Brunner, H.G., Schuurs-Hoeijmakers, J.H.M., Landsverk, M.L., Foulds, N., Kukolich, M.K., Gavrilova, R.H., Greville-Heygate, S., Hanson-Kahn, A., Bernstein, J.A., Glass, J., Chitayat, D., Burrow, T.A., Husami, A., Collins, K., Wusik, K., Aa, N. van der, Kooy, F., Brown, K.T., Gadzicki, D., Kini, U., Alvarez, S., Fernandez-Jaen, A., McGehee, F., Selby, K., Tarailo-Graovac, M., Allen, M., Karnebeek, C.D. van, Stavropoulos, D.J., Marshall, C.R., Merico, D., Gregor, A., Zweier, C., Hopkin, R.J., Chu, Y.W., Chung, B.H., Vries, B. de, Devriendt, K., Hurles, M.E., and Brunner, H.G.

Abstract

Contains fulltext : 167655.pdf (publisher's version ) (Closed access), We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual "wavy" profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases.

Published
2016

37. Clinical delineation of the PACS1-related syndrome--Report on 19 patients

Author

Schuurs-Hoeijmakers, J.H.M., Landsverk, M.L., Foulds, N., Kukolich, M.K., Gavrilova, R.H., Greville-Heygate, S., Hanson-Kahn, A., Bernstein, J.A., Glass, J., Chitayat, D., Burrow, T.A., Husami, A., Collins, K., Wusik, K., Aa, N. van der, Kooy, F., Brown, K.T., Gadzicki, D., Kini, U., Alvarez, S., Fernandez-Jaen, A., McGehee, F., Selby, K., Tarailo-Graovac, M., Allen, M., Karnebeek, C.D. van, Stavropoulos, D.J., Marshall, C.R., Merico, D., Gregor, A., Zweier, C., Hopkin, R.J., Chu, Y.W., Chung, B.H., Vries, B. de, Devriendt, K., Hurles, M.E., Brunner, H.G., Schuurs-Hoeijmakers, J.H.M., Landsverk, M.L., Foulds, N., Kukolich, M.K., Gavrilova, R.H., Greville-Heygate, S., Hanson-Kahn, A., Bernstein, J.A., Glass, J., Chitayat, D., Burrow, T.A., Husami, A., Collins, K., Wusik, K., Aa, N. van der, Kooy, F., Brown, K.T., Gadzicki, D., Kini, U., Alvarez, S., Fernandez-Jaen, A., McGehee, F., Selby, K., Tarailo-Graovac, M., Allen, M., Karnebeek, C.D. van, Stavropoulos, D.J., Marshall, C.R., Merico, D., Gregor, A., Zweier, C., Hopkin, R.J., Chu, Y.W., Chung, B.H., Vries, B. de, Devriendt, K., Hurles, M.E., and Brunner, H.G.

Abstract

Contains fulltext : 167655.pdf (Publisher’s version ) (Open Access), We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual "wavy" profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases.

Published
2016

38. Exome Sequencing and the Management of Neurometabolic Disorders

Author

Tarailo-Graovac, M., Shyr, C., Ross, C.J., Horvath, G.A., Salvarinova, R., Ye, X.C., Zhang, L.H., Bhavsar, A.P., Lee, J.J., Drögemöller, B.I., Abdelsayed, M., Alfadhel, M., Armstrong, L., Baumgartner, M.R., Burda, P., Connolly, M.B., Cameron, J., Demos, M., Dewan, T., Dionne, J., Evans, A.M., Friedman, J.M., Garber, I., Lewis, S., Ling, J., Mandal, R., Mattman, A., McKinnon, M., Michoulas, A., Metzger, D., Ogunbayo, O.A., Rakic, B., Rozmus, J., Ruben, P., Sayson, B., Santra, S., Schultz, K.R., Selby, K., Shekel, P., Sirrs, S., Skrypnyk, C., Superti-Furga, A., Turvey, S.E., Allen, M.I. van, Wishart, D., Wu, J., Zafeiriou, D., Kluijtmans, L.A.J., Wevers, R.A., Eydoux, P., Lehman, A.M., Vallance, H., Stockler-Ipsiroglu, S., Sinclair, G., Wasserman, W.W., Karnebeek, C.D. van, Tarailo-Graovac, M., Shyr, C., Ross, C.J., Horvath, G.A., Salvarinova, R., Ye, X.C., Zhang, L.H., Bhavsar, A.P., Lee, J.J., Drögemöller, B.I., Abdelsayed, M., Alfadhel, M., Armstrong, L., Baumgartner, M.R., Burda, P., Connolly, M.B., Cameron, J., Demos, M., Dewan, T., Dionne, J., Evans, A.M., Friedman, J.M., Garber, I., Lewis, S., Ling, J., Mandal, R., Mattman, A., McKinnon, M., Michoulas, A., Metzger, D., Ogunbayo, O.A., Rakic, B., Rozmus, J., Ruben, P., Sayson, B., Santra, S., Schultz, K.R., Selby, K., Shekel, P., Sirrs, S., Skrypnyk, C., Superti-Furga, A., Turvey, S.E., Allen, M.I. van, Wishart, D., Wu, J., Zafeiriou, D., Kluijtmans, L.A.J., Wevers, R.A., Eydoux, P., Lehman, A.M., Vallance, H., Stockler-Ipsiroglu, S., Sinclair, G., Wasserman, W.W., and Karnebeek, C.D. van

Abstract

Item does not contain fulltext

Published
2016

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