Detection of G1138A Mutation of the FGFR3 Gene in Tooth Material from a 180-Year-Old Museological Achondroplastic Skeleton

Kim, Yong‐Chul; Naue, Jana; Rooy, Laurens de; Oostra, Roelof‐Jan

doi:10.3390/genes8090214

Cited by 7 publications

(7 citation statements)

References 31 publications

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“…The historic, 180-year-old skeleton of an achondroplastic adult male is currently curated at the Museum Vrolik, the Anatomical Museum of the University of Amsterdam, The Netherlands. Boer and colleagues [11] were able to extract nuclear DNA from a premolar and identi ed the Gly380Arg mutation of the FGFR3 gene, which is pathognomonic for achondroplasia.…”

Section: Resultsmentioning

confidence: 99%

“…Historical human remains are often part of anatomical collections in universities and museums [17] [4]. Despite their sometimes less than ideal preservation, they "can yield valuable contributions in e.g., etiopathogenetic issues and potentially expand the literature beyond the restrictions of single case studies due to the plurality of specimens with similar anomalies in these collections" ( [11] page 6). However, often, from today's perspective, the provenance of such human remains from historical collections may be ethically questionable.…”

Section: Archaeological Human Remains (Skeletons Mummies) As Objectiv...mentioning

confidence: 99%

“…Archaeological human skeletal remains could be sampled for further genetic research on their speci c disease. The probability of nding the same genetic mutation in ancient and recent disease cases is high if the disease is pathognomonic, e.g., achondroplasia [11]. However, this assumption cannot be regarded as certain and must be tested using a larger reference sample group.…”

Section: Medicalmentioning

confidence: 99%

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The Digital Atlas of Ancient Rare Diseases (DAARD) and its relevance for current research

Gresky,

Frotscher,

Dorn

et al. 2024

Preprint

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Background The history of rare diseases is largely unknown. Research on this topic has focused on individual cases of prominent (historical) individuals and artistic (e.g., iconographic) representations. Medical collections include large numbers of specimens that exhibit signs of rare diseases, but most of these date to relatively recent periods. However, cases of rare diseases detected in mummies and skeletal remains from archaeological excavations have also been recorded. Nevertheless, this direct evidence from historical and archaeological contexts is mainly absent from academic discourse and generally not consulted in medical research on rare diseases. Results This desideratum is addressed by the Digital Atlas of Ancient Rare Diseases (DAARD: https://daard.dainst.org), which is an open access/open data database and web-based mapping tool that collects evidence of different rare diseases found in skeletons and mummies from all over the world and throughout all historic and prehistoric time periods. Disease or individual data, the preservation level of human remains, research methodology, and information about places of curation and literature references are easy to search for. In this manuscript, the design and functionality of the DAARD are illustrated through the example of achondroplasia and other types of stunted growth. Conclusions As an open, collaborative repository for collecting, mapping and querying well-structured medical data on individuals from ancient times, the DAARD opens new research avenues. The number of rare diseases can increase by adding new cases from a variety of backgrounds such as museum collections and archaeological excavations. Depending on the research question, phenotypic or genetic information can be retrieved, as well as information on the general occurrence of a rare disease in selected space–time intervals. Furthermore, for individuals diagnosed with a rare disease, this approach helps them to build identity and reveal an aspect of their rare disease that they may not have been previously aware of. Thus, the DAARD contributes to the understanding of rare diseases from a long-term perspective and adds to the latest relevant research.

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Section: Resultsmentioning

confidence: 99%

Section: Archaeological Human Remains (Skeletons Mummies) As Objectiv...mentioning

confidence: 99%

Section: Medicalmentioning

confidence: 99%

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The Digital Atlas of Ancient Rare Diseases (DAARD) and its relevance for current research

Gresky,

Frotscher,

Dorn

et al. 2024

Preprint

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“…Two 18th and 19th century skeletons of extremely tall individuals had sufficiently intact DNA for targeted PCR of gigantism-associated loci 23,2425 . A pathological achondroplasia mutation in the FGFR3 gene has also been identified in 180-year old remains 26 .…”

Section: Main Textmentioning

confidence: 99%

Millennium-old Pathogenic Mendelian Mutation Discovery for Multiple Osteochondromas from a Gaelic Medieval Graveyard

Jackson

Mattiangeli

Cassidy

et al. 2022

Preprint

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Only a limited number of genetic diseases are diagnosable in archaeological individuals and none have had causal mutations identified in genome-wide screens. Two individuals from the Gaelic Irish Medieval burial ground of Ballyhanna, Co. Donegal, showed evidence of bone tumors consistent with the autosomal dominant condition multiple osteochondromas. Genome sequencing of the earlier individual uncovered a missense mutation in the second exon of EXT1, a specific lesion that has been identified in several modern patients. The later individual lacked this but displayed a novel frameshift mutation leading to a premature stop codon and loss of function in the same gene. These molecular confirmations of a paleopathological diagnosis within a single rural ancient context are surprisingly disjunct, given the observation of clusters of this disease in modern isolated populations and a de novo mutation rate of only 10%.

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“…For example, an 18th century skeleton of an extremely tall individual had sufficiently intact DNA for targeted PCR of a gigantism-associated locus( 14 ). A pathological achondroplasia mutation in the FGFR3 gene has also been identified in 180-year old remains( 15 ).…”

mentioning

confidence: 99%

Millennium-old pathogenic Mendelian mutation discovery for multiple osteochondromas from a Gaelic Medieval graveyard

et al. 2022

View full text Add to dashboard Cite

Only a limited number of genetic diseases are diagnosable in archaeological individuals and none have had causal mutations identified in genome-wide screens. Two individuals from the Gaelic Irish Medieval burial ground of Ballyhanna, Co. Donegal, showed evidence of bone tumours consistent with the autosomal dominant condition multiple osteochondromas. Genome sequencing of the earlier individual uncovered a missense mutation in the second exon of EXT1 , a specific lesion that has been identified in several modern patients. The later individual lacked this but displayed a novel frameshift mutation leading to a premature stop codon and loss of function in the same gene. These molecular confirmations of a paleopathological diagnosis within a single rural ancient context are surprisingly disjunct, given the observation of clusters of this disease in modern isolated populations and a de novo mutation rate of only 10%.

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Detection of G1138A Mutation of the FGFR3 Gene in Tooth Material from a 180-Year-Old Museological Achondroplastic Skeleton

Cited by 7 publications

References 31 publications

The Digital Atlas of Ancient Rare Diseases (DAARD) and its relevance for current research

The Digital Atlas of Ancient Rare Diseases (DAARD) and its relevance for current research

Millennium-old Pathogenic Mendelian Mutation Discovery for Multiple Osteochondromas from a Gaelic Medieval Graveyard

Millennium-old pathogenic Mendelian mutation discovery for multiple osteochondromas from a Gaelic Medieval graveyard

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