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Neuropediatrics 2020; 51(06): 430-434
DOI: 10.1055/s-0040-1710526
Short Communication

Expanding Clinical Phenotype of TRAPPC12-Related Childhood Encephalopathy: Two Cases and Review of Literature

Ayca Dilruba Aslanger 
1   Department of Medical Genetics, Faculty of Medicine, Bezmialem Vakıf University, Istanbul, Turkey
,
Emine Demiral
2   Department of Medical Genetics, Istanbul Training and Research Hospital, Istanbul, Turkey
,
Seyma Sonmez-Sahin
3   Department of Pediatric Neurology, Faculty of Medicine, Bezmialem Vakıf University, Istanbul, Turkey
,
Serhat Guler
4   Department of Pediatric Neurology, Cerrahpasa Faculty of Medicine Hospital, Istanbul University, Istanbul, Turkey
,
Beyza Goncu
5   Experimental Research Center, Bezmialem Vakıf University, Istanbul, Turkey
,
Emrah Yucesan
6   Institute of Life Sciences and Biotechnology, Bezmialem Vakıf University, Istanbul, Turkey
,
Akın Iscan
3   Department of Pediatric Neurology, Faculty of Medicine, Bezmialem Vakıf University, Istanbul, Turkey
,
Sema Saltik
4   Department of Pediatric Neurology, Cerrahpasa Faculty of Medicine Hospital, Istanbul University, Istanbul, Turkey
,
Gozde Yesil
1   Department of Medical Genetics, Faculty of Medicine, Bezmialem Vakıf University, Istanbul, Turkey
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Abstract

Biallelic mutations in the TRAPPC12 gene are responsible for early-onset progressive encephalopathy with brain atrophy and spasticity (PEBAS). To date, three different allelic variants have been reported. Next-generation sequencing allowed discovery of unique alternations in this gene with different phenotypes. We report two patients carrying TRAPPC12 variants, one previously reported and one unknown mutation, with severe neurodevelopmental delay and brain atrophy. Standard clinical examination and cranial imaging studies were performed in these two unrelated patients. In addition, whole-exome sequencing was performed, followed by Sanger sequencing for verification. The first patient, a 2-year-old boy, was found to be homozygous for the previously reported c.1880C > T (p.Ala627Val) mutation. He presented with a phenotype including severe progressive cortical atrophy, moderate cerebellar atrophy, epilepsy, and microcephaly, very similar to the previously reported cases. The second case, a 9-year-old boy, carried a novel homozygous c.679T > G (p.Phe227Val) variant and presented with mild cortical atrophy, severe cerebellar atrophy, and neither clinically manifest epilepsy nor microcephaly, which were previously considered typical findings in PEBAS with TRAPPC12 mutations. Our findings suggest that clinical and brain imaging findings might be more variable than previously anticipated; however, a larger number of observations would benefit for broader phenotypic spectrum.

Keywords

brain atrophy - cerebellar atrophy - microcephaly - TRAPPopathies - TRAPPC12 mutation


Publication History

Received: 16 September 2019

Accepted: 12 March 2020

Article published online:
05 May 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References

  • 1 Stromme P, Kanavin OJ, Abdelnoor M. et al. Incidence rates of progressive childhood encephalopathy in Oslo, Norway: a population based study. BMC Pediatr 2007; 7: 25
    CrossrefPubMedGoogle Scholar
  • 2 Hussain SA. Epileptic encephalopathies. Continuum (Minneap Minn) 2018; 24 (1, Child Neurology): 171-185
    PubMedGoogle Scholar
  • 3 Surtees R. Understanding neurodegenerative disorders. Curr Paediatr 2002; 12: 191-198
    CrossrefPubMedGoogle Scholar
  • 4 Milev MP, Grout ME, Saint-Dic D. et al. Mutations in TRAPPC12 manifest in progressive childhood encephalopathy and Golgi dysfunction. Am J Hum Genet 2017; 101 (02) 291-299
    CrossrefPubMedGoogle Scholar
  • 5 Kara B, Etiler N, Aydoğan Uncuoğlu A. et al. Head circumference charts for Turkish children aged five to eighteen years. Noro Psikiyatri Arsivi 2016; 53 (01) 55-62
    CrossrefPubMedGoogle Scholar
  • 6 Uvebrant P, Lanneskog K, Hagberg B. The epidemiology of progressive encephalopathies in childhood. I. Live birth prevalence in west Sweden. Neuropediatrics 1992; 23 (04) 209-211
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Orsini A, Zara F, Striano P. Recent advances in epilepsy genetics. Neurosci Lett 2018; 667: 4-9
    CrossrefPubMedGoogle Scholar
  • 8 Rabouille C, Haase G. Editorial: Golgi pathology in neurodegenerative diseases. Front Neurosci 2016; 9: 489
    CrossrefPubMedGoogle Scholar
  • 9 Sacher M, Kim YG, Lavie A, Oh BH, Segev N. The TRAPP complex: insights into its architecture and function. Traffic 2008; 9 (12) 2032-2042
    CrossrefPubMedGoogle Scholar
  • 10 Scrivens PJ, Noueihed B, Shahrzad N, Hul S, Brunet S, Sacher M. C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking. Mol Biol Cell 2011; 22 (12) 2083-2093
    CrossrefPubMedGoogle Scholar
  • 11 Sacher M, Shahrzad N, Kamel H, Milev MP. TRAPPopathies: an emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)-associated proteins. Traffic 2019; 20 (01) 5-26
    CrossrefPubMedGoogle Scholar
  • 12 Gedeon AK, Colley A, Jamieson R. et al. Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. Nat Genet 1999; 22 (04) 400-404
    CrossrefPubMedGoogle Scholar
  • 13 Liang WC, Zhu W, Mitsuhashi S. et al. Congenital muscular dystrophy with fatty liver and infantile-onset cataract caused by TRAPPC11 mutations: broadening of the phenotype. Skelet Muscle 2015; 5: 29-34
    CrossrefPubMedGoogle Scholar
  • 14 Mir A, Kaufman L, Noor A. et al. Identification of mutations in TRAPPC9, which encodes the NIK- and IKK-beta-binding protein, in nonsyndromic autosomal-recessive mental retardation. Am J Hum Genet 2009; 85 (06) 909-915
    CrossrefPubMedGoogle Scholar
  • 15 Milev MP, Sacher M. Mitotic transformation of TRAMM/TRAPPC12. Oncotarget 2015; 6 (20) 17853-17854
    CrossrefPubMedGoogle Scholar