Top

Published in:

01-11-2020 | Minisymposium: Imaging of skeletal dysplasia

Genetics for paediatric radiologists

Authors: Schaida Schirwani, Jennifer Campbell

Published in: Pediatric Radiology | Issue 12/2020

Abstract

An understanding of genetics and genomics is increasingly important for all clinicians. Next-generation genomic sequencing technologies enable sequencing of the entire human genome in short timescales, and are increasingly being implemented in health care systems. Clinicians across all medical specialties will increasingly use results generated from genomic testing to inform their clinical practice and provide the best quality of care for patients. These innovations are already transforming the diagnostic pathways for rare genetic diseases, including skeletal dysplasias, with an inevitable impact on the traditional roles of diagnosticians. This article covers the fundamentals of human genetics, mechanisms of genetic variation and the technologies used to investigate the genetic basis of disease, with a specific focus on skeletal dysplasias and the potential impact of genomics on paediatric radiology.

Turnbull C, Scott RH, Thomas E et al (2018) The 100 000 genomes project: bringing whole genome sequencing to the NHS. BMJ 361:k1687CrossRefPubMed

Bonafe L, Cormier-Daire V, Hall C et al (2015) Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A 167A:2869–2892CrossRefPubMed

Lazarus S, Zankl A, Duncan EL (2014) Next-generation sequencing: a frameshift in skeletal dysplasia gene discovery. Osteoporos Int 25:407–422CrossRefPubMed

Boycott KM, Vanstone MR, Bulman DE, MacKenzie AE (2013) Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nat Rev Genet 14:681–691CrossRefPubMed

Lettice LA, Heaney SJH, Purdie LA et al (2003) A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet 12:1725–1735CrossRefPubMed

Lupianez DG, Kraft K, Heinrich V et al (2015) Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161:1012–1025CrossRefPubMedPubMedCentral

Estrada K, Styrkarsdottir U, Evangelou E et al (2012) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 44:491–501CrossRefPubMedPubMedCentral

Klopocki E, Lohan S, Doelken SC et al (2012) Duplications of BHLHA9 are associated with ectrodactyly and tibia hemimelia inherited in non-Mendelian fashion. J Med Genet 49:119–125CrossRefPubMed

Daugherty A (2017) Achondroplasia: etiology, clinical presentation, and management. Neonatal Netw 36:337–342CrossRefPubMed

10.

Wright MJ, Irving MD (2012) Clinical management of achondroplasia. Arch Dis Child 97:129–134CrossRefPubMed

11.

Goriely A, Wilkie AOM (2012) Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. Am J Hum Genet 90:175–200CrossRefPubMedPubMedCentral

12.

Barros NMT, Hoac B, Neves RL et al (2013) Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia. J Bone Miner Res 28:688–699CrossRefPubMed

13.

Pansuriya TC, Kroon HM, Bovee JVMG (2010) Enchondromatosis: insights on the different subtypes. Int J Clin Exp Pathol 3:557–569PubMedPubMedCentral

14.

Pansuriya TC, van Eijk R, d'Adamo P et al (2011) Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet 43:1256–1261CrossRefPubMedPubMedCentral

15.

Couvineau A, Wouters V, Bertrand G et al (2008) PTHR1 mutations associated with Ollier disease result in receptor loss of function. Hum Mol Genet 17:2766–2775CrossRefPubMedPubMedCentral

16.

Gajecka M (2016) Unrevealed mosaicism in the next-generation sequencing era. Mol Gen Genomics 291:513–530CrossRef

17.

Zilina O, Koltsina M, Raid R et al (2015) Somatic mosaicism for copy-neutral loss of heterozygosity and DNA copy number variations in the human genome. BMC Genomics 16:703CrossRefPubMedPubMedCentral

18.

Wright CF, FitzPatrick DR, Firth HV (2018) Paediatric genomics: diagnosing rare disease in children. Nat Rev Genet 19:253–268CrossRefPubMed

19.

Heather JM, Chain B (2016) The sequence of sequencers: the history of sequencing DNA. Genomics 107:1–8CrossRefPubMed

20.

Kohler S, Doelken SC, Mungall CJ et al (2014) The human phenotype ontology project: linking molecular biology and disease through phenotype data. Nucleic Acids Res 42:D966–D974CrossRefPubMed

21.

Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424CrossRefPubMedPubMedCentral

22.

Offiah AC, Hall CM (2019) The radiologic diagnosis of skeletal dysplasias: past, present and future. Pediatr Radiol. https://doi.org/10.1007/s00247-019-04533-y

23.

Ain NU, Makitie O, Naz S (2018) Autosomal recessive chondrodysplasia with severe short stature caused by a biallelic COL10A1 variant. J Med Genet 55:403–407CrossRefPubMed

24.

Taylan F, Makitie O (2016) Abnormal proteoglycan synthesis due to gene defects causes skeletal diseases with overlapping phenotypes. Horm Metab Res 48:745–754CrossRefPubMed

Title: Genetics for paediatric radiologists
Authors: Schaida Schirwani
Jennifer Campbell
Publication date: 01-11-2020
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Radiology / Issue 12/2020
Print ISSN: 0301-0449
Electronic ISSN: 1432-1998
DOI: https://doi.org/10.1007/s00247-020-04837-4

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Genetics for paediatric radiologists

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 12/2020

MRI of tibial stress fractures: relationship between Fredericson classification and time to recovery in pediatric athletes

Assistant editor transitions: thank you, thank you, thank you (and welcome ×3!)

Inna Nitz, MD (1932–2020)

European overview of current practice of fetal imaging by pediatric radiologists: a new task force is launched

Outpacing movement — ultrafast volume coverage in neuropediatric magnetic resonance imaging

Ultrasonography in pediatric Budd–Chiari syndrome