The Experts below are selected from a list of 1227 Experts worldwide ranked by ideXlab platform
Frauke Hornemann - One of the best experts on this subject based on the ideXlab platform.
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congenital cervical Spine Malformation due to bi allelic ripply2 variants in spondylocostal dysostosis type 6
Clinical Genetics, 2021Co-Authors: Meret Wegler, Christian L Roth, E Schumann, Jillene Kogan, Ellen Totten, Maria Guillen J Sacoto, Rami Abou Jamra, Frauke HornemannAbstract:RIPPLY2 is an essential part of the formation of somite patterning during embryogenesis and in establishment of rostro-caudal polarity. Here, we describe three individuals from two families with compound-heterozygous variants in RIPPLY2 (NM_001009994.2): c.238A > T, p.(Arg80*) and c.240-4 T > G, p.(?), in two 15 and 20 year old sisters, and a homozygous nonsense variant, c.238A > T, p.(Arg80*), in an 8 year old boy. All patients had multiple vertebral body Malformations in the cervical and thoracic region, small or absent rib involvement, myelopathies, and common clinical features of SCDO6 including scoliosis, mild facial asymmetry, spinal spasticity and hemivertebrae. The nonsense variant can be classified as likely pathogenic based on the ACMG criteria while the splice variants must be classified as a variant of unknown significance. With this report on two further families, we confirm RIPPLY2 as the gene for SCDO6 and broaden the phenotype by adding myelopathy with or without spinal canal stenosis and spinal spasticity to the symptom spectrum. This article is protected by copyright. All rights reserved.
Meret Wegler - One of the best experts on this subject based on the ideXlab platform.
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congenital cervical Spine Malformation due to bi allelic ripply2 variants in spondylocostal dysostosis type 6
Clinical Genetics, 2021Co-Authors: Meret Wegler, Christian L Roth, E Schumann, Jillene Kogan, Ellen Totten, Maria Guillen J Sacoto, Rami Abou Jamra, Frauke HornemannAbstract:RIPPLY2 is an essential part of the formation of somite patterning during embryogenesis and in establishment of rostro-caudal polarity. Here, we describe three individuals from two families with compound-heterozygous variants in RIPPLY2 (NM_001009994.2): c.238A > T, p.(Arg80*) and c.240-4 T > G, p.(?), in two 15 and 20 year old sisters, and a homozygous nonsense variant, c.238A > T, p.(Arg80*), in an 8 year old boy. All patients had multiple vertebral body Malformations in the cervical and thoracic region, small or absent rib involvement, myelopathies, and common clinical features of SCDO6 including scoliosis, mild facial asymmetry, spinal spasticity and hemivertebrae. The nonsense variant can be classified as likely pathogenic based on the ACMG criteria while the splice variants must be classified as a variant of unknown significance. With this report on two further families, we confirm RIPPLY2 as the gene for SCDO6 and broaden the phenotype by adding myelopathy with or without spinal canal stenosis and spinal spasticity to the symptom spectrum. This article is protected by copyright. All rights reserved.
Lu Hao - One of the best experts on this subject based on the ideXlab platform.
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CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays
2017Co-Authors: Windpassinger Christian, Piard Juliette, Bonnard Carine, Alfadhel Majid, Lim Shuhui, Bisteau Xavier, Blouin Stéphane, Ali, Nur'ain B., Ng, Alvin Yu Jin, Lu HaoAbstract:In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, Spine Malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal developmen
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CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays.
'Elsevier BV', 2017Co-Authors: Windpassinger Christian, Piard Juliette, Bonnard Carine, Alfadhel Majid, Lim Shuhui, Bisteau Xavier, Blouin Stéphane, Ali, Nur'ain B., Ng, Alvin Yu Jin, Lu HaoAbstract:In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, Spine Malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development.info:eu-repo/semantics/publishe
Ellen Totten - One of the best experts on this subject based on the ideXlab platform.
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congenital cervical Spine Malformation due to bi allelic ripply2 variants in spondylocostal dysostosis type 6
Clinical Genetics, 2021Co-Authors: Meret Wegler, Christian L Roth, E Schumann, Jillene Kogan, Ellen Totten, Maria Guillen J Sacoto, Rami Abou Jamra, Frauke HornemannAbstract:RIPPLY2 is an essential part of the formation of somite patterning during embryogenesis and in establishment of rostro-caudal polarity. Here, we describe three individuals from two families with compound-heterozygous variants in RIPPLY2 (NM_001009994.2): c.238A > T, p.(Arg80*) and c.240-4 T > G, p.(?), in two 15 and 20 year old sisters, and a homozygous nonsense variant, c.238A > T, p.(Arg80*), in an 8 year old boy. All patients had multiple vertebral body Malformations in the cervical and thoracic region, small or absent rib involvement, myelopathies, and common clinical features of SCDO6 including scoliosis, mild facial asymmetry, spinal spasticity and hemivertebrae. The nonsense variant can be classified as likely pathogenic based on the ACMG criteria while the splice variants must be classified as a variant of unknown significance. With this report on two further families, we confirm RIPPLY2 as the gene for SCDO6 and broaden the phenotype by adding myelopathy with or without spinal canal stenosis and spinal spasticity to the symptom spectrum. This article is protected by copyright. All rights reserved.
Rami Abou Jamra - One of the best experts on this subject based on the ideXlab platform.
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congenital cervical Spine Malformation due to bi allelic ripply2 variants in spondylocostal dysostosis type 6
Clinical Genetics, 2021Co-Authors: Meret Wegler, Christian L Roth, E Schumann, Jillene Kogan, Ellen Totten, Maria Guillen J Sacoto, Rami Abou Jamra, Frauke HornemannAbstract:RIPPLY2 is an essential part of the formation of somite patterning during embryogenesis and in establishment of rostro-caudal polarity. Here, we describe three individuals from two families with compound-heterozygous variants in RIPPLY2 (NM_001009994.2): c.238A > T, p.(Arg80*) and c.240-4 T > G, p.(?), in two 15 and 20 year old sisters, and a homozygous nonsense variant, c.238A > T, p.(Arg80*), in an 8 year old boy. All patients had multiple vertebral body Malformations in the cervical and thoracic region, small or absent rib involvement, myelopathies, and common clinical features of SCDO6 including scoliosis, mild facial asymmetry, spinal spasticity and hemivertebrae. The nonsense variant can be classified as likely pathogenic based on the ACMG criteria while the splice variants must be classified as a variant of unknown significance. With this report on two further families, we confirm RIPPLY2 as the gene for SCDO6 and broaden the phenotype by adding myelopathy with or without spinal canal stenosis and spinal spasticity to the symptom spectrum. This article is protected by copyright. All rights reserved.