Severe congenital microcephaly with AP4M1 mutation, a case report

BMC Medical Genetics

Laurence Desmyter¹  Philippe David²  Helene Verhelst³  Isabelle Pirson⁴  Sarah Duerinckx⁴  Marc Abramowicz⁴  Camille Perazzolo⁴ 

[1] Department of Medical Genetics, Hôpital Erasme – Université Libre de Bruxelles;Department of Medical Imaging and Radiology, Hôpital Erasme – Université Libre de Bruxelles;Department of Paediatric Neurology, Ghent University Hospital;IRIBHM, Université Libre de Bruxelles;

关键词: Exome sequencing;    Brain development;    Consanguinity;    Intellectual disability;    Case report;   

DOI  :  10.1186/s12881-017-0412-9

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown