Microcephaly primary hereditary (MCPH): Report of novel ASPM variants and prenatal diagnosis in a Vietnamese family

• Published in: Taiwanese Journal of Obstetrics & Gynecology
• Main Authors: Thinh Huy Tran, Quang Minh Diep, My Ha Cao, Long Hoang Luong, Van Anh Pham, Oanh Thi Lan Dinh, The-Hung Bui, Thanh Van Ta, Van Khanh Tran
• Format: Article
• Language: English
• Published: Elsevier 2021-09-01
• Subjects: Microcephaly primary hereditary; ASPM; MCPH5; Exome sequencing
• Online Access: http://www.sciencedirect.com/science/article/pii/S1028455921001947
• ISSN: 1028-4559

Objective: MCPH (microcephaly primary hereditary) is a group of autosomal recessive developmental disorders with microcephaly present at birth and intellectual disability. Since a second trimester ultrasound is not able to detect subtypes with minimal prenatal presentations, only prenatal diagnosis by genetic testing can confirm these cases and allow for effective genetic counseling, especially a family with a previously affected child. Case Report: A 37-year-old women was pregnant for the third time and had two prior children with profound microcephaly and mental retardation. Targeted panel sequencing identified novel compound heterozygous ASPM pathogenic variants: c.1615_1616del (p. Glu539ArgfsTer15); c.∗293T > A (p. Leu98Ter), which confirmed the diagnosis of MCPH5 (#OMIM 608716). Genetic testing was conducted for family members and applied on prenatal diagnosis. Conclusion: This is the first cases of MCPH5 to be reported in Vietnam and the genetic result aided in prenatal diagnosis of a high-risk pregnancy. The study highlights the importance of genetic testing in defining definitive diagnosis which allowed for timely prenatal diagnosis and genetic counseling for the family.