• Hajar Aryan, Shaghayegh Zokaei, Dariush Farhud, Mohammad Keykhaei, Mahmoud Reza Ashrafi, Maryam Rasulinezhad, Seyyed Mohammad Mahdi Hosseini, Ehsan Razmara, and Ali Reza Tavasoli.
• National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
• Ir J Med Sci. 2022 Dec 1; 191 (6): 273327412733-2741.

BackgroundMicrocephaly is a prominent feature of patients with primary autosomal recessive microcephaly 2 (MCPH2) caused by mutations in the WD Repeat Domain 62 (WDR62; OMIM: 613,583).AimThe study aimed to identify the underlying genetic factor(s) causing microcephaly in two patients in a consanguineous Iranian family.MethodsTwo male patients (11 and 27 years old) were noticed due to microcephaly, neurodevelopmental delay, and occasional seizures. The younger patient (the proband) was subjected to paired-end whole-exome sequencing followed by Sanger sequencing to detect any underlying genetic factor.ResultsUpon examination, both patients showed microcephaly as a prominent manifestation; they were under-weighted as well. The patients had a moderate gross motor impairment, severe cognitive disability and speech delay, increased deep tendon reflexes, flexible joint contractures, sensorineural hearing loss, and vertical nystagmus as a new ocular finding. The proband had more severe neurodevelopmental delay symptoms. The brain magnetic resonance imaging series revealed severe structural and cortical brain abnormalities in addition to hemiatrophy. Using Whole-exome Sequencing, a novel homozygous missense variant-NM_001083961.2; c.1598A > G: p.(His533Arg)-was identified in the WDR62. Subsequently, in silico analyses determined the possible impacts of the novel variant on the structure and function of WDR62 protein.ConclusionsHerein, we identified a novel homozygous missense variant in the WDR62 in two patients with MCPH2. Vertical nystagmus and sensorineural hearing loss were detected as novel neurological findings. The present study expands the phenotype and genotype spectrum of MCPH2.© 2021. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.

26 keywords...

hide…