Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1
We describe two brothers who presented at birth with bone growth abnormalities, followed by development of increasingly severe intellectual and physical disability, growth restriction, epilepsy, and cerebellar and brain stem atrophy, but normal ocular phenotypes. Case 1 died at 19 years of age due t...
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Wiley
2015-01-01
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| Series: | Case Reports in Genetics |
| Online Access: | http://dx.doi.org/10.1155/2015/454526 |
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| author | Jessie C. Jacobsen Emma Glamuzina Juliet Taylor Brendan Swan Shona Handisides Callum Wilson Michael Fietz Tessa van Dijk Bart Appelhof Rosamund Hill Rosemary Marks Donald R. Love Stephen P. Robertson Russell G. Snell Klaus Lehnert |
| author_facet | Jessie C. Jacobsen Emma Glamuzina Juliet Taylor Brendan Swan Shona Handisides Callum Wilson Michael Fietz Tessa van Dijk Bart Appelhof Rosamund Hill Rosemary Marks Donald R. Love Stephen P. Robertson Russell G. Snell Klaus Lehnert |
| author_sort | Jessie C. Jacobsen |
| collection | DOAJ |
| description | We describe two brothers who presented at birth with bone growth abnormalities, followed by development of increasingly severe intellectual and physical disability, growth restriction, epilepsy, and cerebellar and brain stem atrophy, but normal ocular phenotypes. Case 1 died at 19 years of age due to chronic respiratory illnesses without a unifying diagnosis. The brother remains alive but severely disabled at 19 years of age. Whole exome sequencing identified compound heterozygous stop mutations in the peroxisome biogenesis factor 7 gene in both individuals. Mutations in this gene cause rhizomelic chondrodysplasia punctata, type 1 (RCDP1). One mutation, p.Arg232∗, has only been documented once before in a Japanese family, which is of interest given these two boys are of European descent. The other mutation, p.Leu292∗, is found in approximately 50% of RCDP1 patients. These are the first cases of RCDP1 that describe the coinheritance of the p.Arg232∗ and p.Leu292∗ mutations and demonstrate the utility of WES in cases with unclear diagnoses. |
| format | Article |
| id | doaj-art-18e81e69ad624ba4aee1b55089870ac8 |
| institution | Kabale University |
| issn | 2090-6544 2090-6552 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Genetics |
| spelling | doaj-art-18e81e69ad624ba4aee1b55089870ac82025-02-03T01:10:29ZengWileyCase Reports in Genetics2090-65442090-65522015-01-01201510.1155/2015/454526454526Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1Jessie C. Jacobsen0Emma Glamuzina1Juliet Taylor2Brendan Swan3Shona Handisides4Callum Wilson5Michael Fietz6Tessa van Dijk7Bart Appelhof8Rosamund Hill9Rosemary Marks10Donald R. Love11Stephen P. Robertson12Russell G. Snell13Klaus Lehnert14Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandAdult and Paediatric National Metabolic Service, Auckland City Hospital, Auckland 1142, New ZealandGenetic Health Service New Zealand, Auckland City Hospital, Auckland 1142, New ZealandCentre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandDepartment of Radiology, Auckland City Hospital, Auckland 1142, New ZealandAdult and Paediatric National Metabolic Service, Auckland City Hospital, Auckland 1142, New ZealandDepartment of Biochemical Genetics, SA Pathology, North Adelaide, SA 5006, AustraliaDepartment of Genome Analysis, Academic Medical Centre, 1105 Amsterdam, NetherlandsDepartment of Genome Analysis, Academic Medical Centre, 1105 Amsterdam, NetherlandsDepartment of Neurology, Auckland City Hospital, Auckland 1142, New ZealandDevelopmental Paediatric Service, Starship Children’s Health, Auckland 1142, New ZealandDiagnostic Genetics, LabPLUS, Auckland City Hospital, Auckland 1142, New ZealandDunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandCentre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandCentre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandWe describe two brothers who presented at birth with bone growth abnormalities, followed by development of increasingly severe intellectual and physical disability, growth restriction, epilepsy, and cerebellar and brain stem atrophy, but normal ocular phenotypes. Case 1 died at 19 years of age due to chronic respiratory illnesses without a unifying diagnosis. The brother remains alive but severely disabled at 19 years of age. Whole exome sequencing identified compound heterozygous stop mutations in the peroxisome biogenesis factor 7 gene in both individuals. Mutations in this gene cause rhizomelic chondrodysplasia punctata, type 1 (RCDP1). One mutation, p.Arg232∗, has only been documented once before in a Japanese family, which is of interest given these two boys are of European descent. The other mutation, p.Leu292∗, is found in approximately 50% of RCDP1 patients. These are the first cases of RCDP1 that describe the coinheritance of the p.Arg232∗ and p.Leu292∗ mutations and demonstrate the utility of WES in cases with unclear diagnoses.http://dx.doi.org/10.1155/2015/454526 |
| spellingShingle | Jessie C. Jacobsen Emma Glamuzina Juliet Taylor Brendan Swan Shona Handisides Callum Wilson Michael Fietz Tessa van Dijk Bart Appelhof Rosamund Hill Rosemary Marks Donald R. Love Stephen P. Robertson Russell G. Snell Klaus Lehnert Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1 Case Reports in Genetics |
| title | Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1 |
| title_full | Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1 |
| title_fullStr | Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1 |
| title_full_unstemmed | Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1 |
| title_short | Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1 |
| title_sort | whole exome sequencing reveals compound heterozygosity for ethnically distinct pex7 mutations responsible for rhizomelic chondrodysplasia punctata type 1 |
| url | http://dx.doi.org/10.1155/2015/454526 |
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