Prenatal Identification of a Novel Mutation in the <i>MCPH1</i> Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) Using Next Generation Sequencing (NGS): A Case Report and Review of the Literature
Second Department of Obstetrics and Gynaecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 112527 Athens, Greece
1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
Maria Papamichail
Postgraduate Programme “Maternal Fetal Medicine”, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
Vassilios Papadopoulos
Department of Obstetrics & Gynecology, University of Patra, 26500 Patras, Greece
Antonios Garas
Department of Gynecology, Larissa Medical School, University of Thessaly, 38221 Larissa, Greece
Sotirios Sotiriou
Department of Clinical Embryology, Larissa Medical School, University of Thessaly, 41334 Larissa, Greece
Ioannis Papastefanou
Fetal Medicine Clinic, Monis Petraki 4, Kolonaki, 11521 Athens, Greece
Georgios Daskalakis
First Department of Obstetrics and Gynaecology, “Alexandra” Maternity Hospital, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece
Aleksandar Ristic
Obstetric and Gynecological Clinic Narodni Front, 11000 Belgrade, Serbia
Background: MCPH1 is known as the microcephalin gene (OMIM: *607117), of which the encoding protein is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptides. There is a strong connection between mutations of the MCPH1 gene and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains, varying levels of mental retardation, delayed speech and poor language skills. Methods: In this article, a family with two affected fetuses presenting a mutation of the MCPH1 gene is reported. During the first trimester ultrasound of the second pregnancy, the measure of nuchal translucency was increased (NT = 3.1 mm) and, therefore, the risk for chromosomal abnormalities was high. Chorionic villi sampling (CVS) was then performed. Afterwards, fetal karyotyping and Next Generation Sequencing were carried out. Afterwards, NGS was also performed in a preserved sample of the first fetus which was terminated due to microcephaly. Results: In this case, the fetuses had a novel homozygous mutation of the MCPH1 gene (c.348del). Their parents were heterozygous for the mutation. The fetuses showed severe microcephaly. Because of the splice sites in introns, this mutation causes the forming of dysfunctional proteins which lack crucial domains of the C-terminus. Conclusion: Our findings portray an association between the new MCPH1 mutation (c.348del) and the clinical features of autosomal recessive primary microcephaly (MCPH), contributing to a broader spectrum related to these pathologies. To our knowledge, this is the first prenatal diagnosis of MCPH due to a novel MCPH1 mutation.
