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Case Reports
. 2021 May 18;14(1):131.
doi: 10.1186/s12920-021-00980-5.

A new family with spastic paraplegia type 51 and novel mutations in AP4E1

Izabela Winkler  1   2 , Paweł Miotła  3 , Monika Lejman  4 , Aleksandra Pietrzyk  5 , Magdalena Kacprzak  5 , Marcin Kubiak  6 , Agnieszka Sobczyńska-Tomaszewska  5 , Maciej Skrzypczak  3 , Ilona Jaszczuk  4   7
Affiliations
Case Reports

A new family with spastic paraplegia type 51 and novel mutations in AP4E1

Izabela Winkler et al. BMC Med Genomics. .

Abstract

Background: Autosomal recessive mutations in the AP-4 (adaptor protein complex 4) complex subunit ϵ - 1 (AP-4E1) gene on chromosome 15q21.2 are known to cause spastic paraplegia 51 (SPG51). The exact phenotype of SPG51 remains poorly characterized, because only a few families have been reported as carriers of the mutation. In addition, a previous study identified an autosomal dominant mutation in the AP4E1 gene as being associated with persistent stuttering. The aim of the current study was to characterize the phenotype of a paediatric patient with an identified novel AP4E1 mutation presenting with significant psychomotor retardation, intellectual disability and paraplegia.

Methods: Magnetic resonance imaging was used to identify hypoplasia of the corpus callosum. The DNA sample was tested using multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). In addition, next-generation sequencing (NGS) was performed using the patient's DNA, and Sanger sequencing was performed using that of his family members.

Results: The phenotype was identified to be associated with a novel pathogenic variant c.942_943 + 3delinsCC in the AP4E1 gene. The patient manifested severely delayed psychomotor development, impaired global physical development and general illness. Movement disorders were evident during the neonatal period.

Conclusions: The present study identifies a previously unknown disease-inducing AP4E1 gene mutation.

Keywords: AP4E1; Cerebral palsy; Genetic disorders; Neurological disorders; Next-generation sequencing; Psychomotor retardation; Spastic paraplegia.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
In silico prediction of the c.942_943 + 3delinsCC (3delTGGTAinsCC) homozygous mutation of the AP4E1 gene in the proband with spastic paraplegia type 51. According to NC_000015.9, NM_001252127.2, NM_007347.5 the sequence is CACATATGGTA
Fig. 2
Fig. 2
Family pedigree. The mutation status of each individual is presented. Three deletion status are indicated: (i) −/−, wild-type; (ii) +/−, unaffected carrier; and (iii) +/+, affected carrier. Year of birth is shown below square or circle
See this image and copyright information in PMC

References

    1. Abou Jamra R, Philippe O, Raas-Rothschild A, et al. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am J Hum Genet. 2011;88:788–795. doi: 10.1016/j.ajhg.2011.04.019. - DOI - PMC - PubMed
    1. Moreno-De-Luca A, Helmers SL, Mao H, Burns TG, Melton AM, Schmidt KR, Fernhoff PM, Ledbetter DH, Martin CL. Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. J Med Genet. 2011;48:141–144. doi: 10.1136/jmg.2010.082263. - DOI - PMC - PubMed
    1. Fletcher NA, Foley J. Parental age, genetic mutation, and cerebral palsy. J Med Genet. 1993;30:44–46. doi: 10.1136/jmg.30.1.44. - DOI - PMC - PubMed
    1. Najmabadi H, Hu H, Garshasbi M, et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011;478:57–63. doi: 10.1038/nature10423. - DOI - PubMed
    1. Dell’Angelica EC, Mullins C, Bonifacino JS. AP-4, a novel protein complex related to Clathrin adaptors. J Biol Chem. 1999;274:7278–7285. doi: 10.1091/mbc.12.7.2075. - DOI - PubMed

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