An atypical presentation of Joubert syndrome due to a novel mutation in ZNF423 gene

ATP1A3 gene mutations can result in a spectrum of diseases with diverse neurological manifestations. One such disorder linked to this mutation is rapid-onset dystonia–parkinsonism (RDP), which manifests as dystonia with features of parkinsonism, such as tremors, rigidity, muscle spasms, and bulbar symptoms. Affected patients are typically adolescents or young adults, with symptoms occurring in a rostrocaudal pattern. We report a unique case of a 2-year-old child with an early onset, atypical presentation of RDP. In addition to motor developmental delay, he presented with muscle rigidity and mild asymmetric dystonia of the limbs, with the lower limbs being more affected than the upper limbs. Genetic sequencing of the child revealed a novel heterozygous autosomal dominant mutation of ATP1A3 gene c.173A>G (p. Tyr58Cys). This report highlights that RDP can present with atypical presentations in the paediatric population and adds to existing medical literature on the clinical spectrum of ATP1A3 genetic channelopathy.

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Atypical Presentation of Gelsolin Amyloidosis in a Man of African Descent with a Novel Mutation in the Gelsolin Gene

American Journal of Case Reports ◽

10.12659/ajcr.907550 ◽

2018 ◽

Vol 19 ◽

pp. 374-381 ◽

Cited By ~ 6

Author(s):

Karlos Z. Oregel ◽

Geoffrey P. Shouse ◽

Cyrus Oster ◽

Freddy Martinez ◽

Jun Wang ◽

...

Keyword(s):

Novel Mutation ◽

African Descent ◽

Atypical Presentation

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Atypical Presentation of Sengers Syndrome: A Novel Mutation Revealed with Postmortem Genetic Testing

Fetal and Pediatric Pathology ◽

10.1080/15513815.2019.1639089 ◽

2019 ◽

Vol 39 (2) ◽

pp. 163-171

Author(s):

Naz Guleray ◽

Can Kosukcu ◽

Zihni Ekim Taskiran ◽

Pelin Ozlem Simsek Kiper ◽

Gulen Eda Utine ◽

...

Keyword(s):

Genetic Testing ◽

Novel Mutation ◽

Atypical Presentation ◽

Sengers Syndrome ◽

Postmortem Genetic Testing

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Diagnosis of Joubert Syndrome 10 in a Fetus with Suspected Dandy-Walker Variant by WES: A Novel Splicing Mutation in OFD1

BioMed Research International ◽

10.1155/2018/4032543 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Siyuan Linpeng ◽

Jing Liu ◽

Jianyan Pan ◽

Yingxi Cao ◽

Yanling Teng ◽

...

Keyword(s):

Autosomal Recessive ◽

Novel Mutation ◽

Joubert Syndrome ◽

Splicing Mutation ◽

The Novel ◽

Rt Pcr ◽

Abnormal Karyotype ◽

Whole Exome ◽

The Family ◽

Sequencing Result

Joubert syndrome (JBTS) is a clinically and genetically heterogeneous group of ciliary diseases. To date, 34 subtypes of JBTS have been classified due to different causative genes or extra clinical features. Most of them are autosomal recessive, while only the subtype 10 (JBTS10) is a quite rare X-linked recessive disorder caused by OFD1 mutations with few reports. In this study, by using whole exome sequencing (WES), a novel OFD1 splicing mutation (c.2488+2T>C) was identified in a male fetus with suspected Dandy-Walker variant (DWV) and syndactyly, for whom abnormal karyotype and pathogenic CNV have been excluded. This mutation was inherited from the mother who has experienced two similar pregnancies before. An abnormal skipping of exon 18 in OFD1 mRNA was confirmed by RT-PCR and sequencing. Result from quantitative RT-PCR also showed that total OFD1 mRNA in the index fetus was significantly lower than the control. After a combined analysis of genetic testing results and genotype-phenotype correlations, the novel mutation c.2488+2T>C in OFD1 was considered to be the genetic cause for the affected fetus. Thus the diagnosis should be JBTS10 rather than the primary clinical diagnosis of DWV. We report the first prenatal case of JBTS10 in Chinese population, which not only helps the family to predict recurrence risks for future pregnancies but also provides more information for understanding such a rare disease. The results also present evidence that WES is an effective method in prenatal diagnosis for those fetuses with Joubert syndrome.

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