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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2017

Open Access 01-12-2017 | Case report

Severe congenital microcephaly with AP4M1 mutation, a case report

Authors: Sarah Duerinckx, Helene Verhelst, Camille Perazzolo, Philippe David, Laurence Desmyter, Isabelle Pirson, Marc Abramowicz

Published in: BMC Medical Genetics | Issue 1/2017

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Abstract

Background

Autosomal recessive defects of either the B1, E1, M1 or S1 subunit of the Adaptor Protein complex-4 (AP4) are characterized by developmental delay, severe intellectual disability, spasticity, and occasionally mild to moderate microcephaly of essentially postnatal onset.

Case presentation

We report on a patient with severe microcephaly of prenatal onset, and progressive spasticity, developmental delay, and severe intellectual deficiency. Exome sequencing showed a homozygous mutation in AP4M1, causing the replacement of an arginine by a stop codon at position 338 of the protein (p.Arg338X). The premature stop codon truncates the Mu homology domain of AP4M1, with predicted loss of function. Exome analysis also showed heterozygous variants in three genes, ATR, MCPH1 and BLM, which are known causes of autosomal recessive primary microcephaly.

Conclusions

Our findings expand the AP4M1 phenotype to severe microcephaly of prenatal onset, and more generally suggest that the AP4 defect might share mechanisms of prenatal neuronal depletion with other genetic defects of brain development causing congenital, primary microcephaly.
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Metadata
Title
Severe congenital microcephaly with AP4M1 mutation, a case report
Authors
Sarah Duerinckx
Helene Verhelst
Camille Perazzolo
Philippe David
Laurence Desmyter
Isabelle Pirson
Marc Abramowicz
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-017-0412-9

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