Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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Two Korean siblings with autosomal recessive spinocerebellar ataxia 20 caused by homozygous variants in SNX14

  • Kim, Ae Ryoung (Department of Rehabilitation Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University) ;
  • Lee, Jong-Mok (Department of Neurology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University) ;
  • Seo, Go Hun (3billion, Inc.) ;
  • Lee, Sang In (Department of Pediatrics, Kyungpook National University Hospital, School of Medicine, Kyungpook National University) ;
  • Bae, Hyunwoo (Department of Pediatrics, Kyungpook National University Hospital, School of Medicine, Kyungpook National University) ;
  • Lee, Yun Jeong (Department of Pediatrics, Kyungpook National University Hospital, School of Medicine, Kyungpook National University)
  • Received : 2021.06.24
  • Accepted : 2021.08.13
  • Published : 2021.12.31
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Abstract

Autosomal recessive spinocerebellar ataxia 20 (SCAR20; OMIM #616354) is a recently described disorder that is characterized by ataxia, intellectual disability, cerebellar atrophy, macrocephaly, coarse face, and absent speech. It is caused by loss-of-function mutations in SNX14. To date, all cases with homozygous pathogenic variants have been identified in consanguineous families. This report describes the first Korean cases of SCAR20 family caused by homozygous variants in SNX14. Two siblings were referred to our clinic because of severe global developmental delay. They presented similar facial features, including a high forehead, long philtrum, thick lips, telecanthus, depressed nasal bridge, and broad base of the nose. Because the older sibling was unable to walk and newly developed ataxia, repeated brain magnetic resonance imaging (MRI) was performed at the age of 4 years, revealing progressive cerebellar atrophy compared with MRI performed at the age of 2 years. The younger sibling's MRI revealed a normal cerebellum at the age of 2 years. Whole-exome sequencing was performed, and homozygous variants, such as c.2746-2A>G, were identified in SNX14 from the older sibling. Sanger sequencing confirmed homozygous SNX14 variants in the two siblings as well as a heterozygous variant in both parents. This report extends our knowledge of the phenotypic and mutational spectrum of SCAR20. We also highlight the importance of deep phenotyping for the diagnosis of SCAR20 in individuals with developmental delay, ataxia, cerebellar atrophy, and distinct facial features.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF-2018R1C1B5085985). The authors would like to express their gratitude to all the patients and family.

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