Hajar Aryan1,2, Shaghayegh Zokaei2,3, Dariush Farhud2,4, Mohammad Keykhaei5, Mahmoud Reza Ashrafi6, Maryam Rasulinezhad7, Seyyed Mohammad Mahdi Hosseini7, Ehsan Razmara8, Ali Reza Tavasoli9. 1. National Institute for Genetic Engineering and Biotechnology, Tehran, Iran. 2. Farhud Medical Genetics Laboratory, Tehran, Iran. 3. School of Advanced Medical Science, Islamic Azad University, Tehran, Iran. 4. School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 5. Endocrinology and Metabolism Population Sciences Institute, Non-Communicable Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran. 6. Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Myelin Disorders Clinic, Tehran University of Medical Sciences, Tehran, Iran. 7. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 8. Australian Regenerative Medicine Institute, Monash University, Melbourne, 3800, Australia. 9. Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Myelin Disorders Clinic, Tehran University of Medical Sciences, Tehran, Iran. a_tavasoli@sina.tums.ac.ir.
Abstract
BACKGROUND: Microcephaly 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). AIM: The study aimed to identify the underlying genetic factor(s) causing microcephaly in two patients in a consanguineous Iranian family. METHODS: Two 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. RESULTS: Upon 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. CONCLUSIONS: Herein, 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.
BACKGROUND: Microcephaly 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). AIM: The study aimed to identify the underlying genetic factor(s) causing microcephaly in two patients in a consanguineous Iranian family. METHODS: Two 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. RESULTS: Upon 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. CONCLUSIONS: Herein, 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.
Authors: Marie A Bogoyevitch; Yvonne Y C Yeap; Zhengdong Qu; Kevin R Ngoei; Yan Y Yip; Teresa T Zhao; Julian I Heng; Dominic C H Ng Journal: J Cell Sci Date: 2012-08-16 Impact factor: 5.285
Authors: Kaya Bilgüvar; Ali Kemal Oztürk; Angeliki Louvi; Kenneth Y Kwan; Murim Choi; Burak Tatli; Dilek Yalnizoğlu; Beyhan Tüysüz; Ahmet Okay Cağlayan; Sarenur Gökben; Hande Kaymakçalan; Tanyeri Barak; Mehmet Bakircioğlu; Katsuhito Yasuno; Winson Ho; Stephan Sanders; Ying Zhu; Sanem Yilmaz; Alp Dinçer; Michele H Johnson; Richard A Bronen; Naci Koçer; Hüseyin Per; Shrikant Mane; Mehmet Necmettin Pamir; Cengiz Yalçinkaya; Sefer Kumandaş; Meral Topçu; Meral Ozmen; Nenad Sestan; Richard P Lifton; Matthew W State; Murat Günel Journal: Nature Date: 2010-08-22 Impact factor: 49.962