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  3. Validation of gene causality for neurological disorders

Validation of gene causality for neurological disorders

Aida M. Bertoli-Avella, MD 1 Zafer Yüksel, MD 1 Halenur Yavuz 1 Caterina Baldi, PhD 1 Anett Marais 1 Jose Maria Garcia-Aznar 1 Nana-Maria Grüning 1 L Abbasi Moheb 1 Omid Paknia, PhD 1 Krishna Kumar Kandaswamy, PhD 1 Martin Werber 1 Maximilian E. R. Weiss 1 Gabriela-Elena Oprea, PhD 1 Fahad Al Hakami 2 Nahla Alshaikh 2 Seham Alameer 2 Aiman Shawli 2 Makia J. Marafi 3 A.A. Elmonairy 3 Fahd Al-Mulla 4 Waleed Al-Twaijri 5 Khalid Al-Thihli 6 AM Al Shamsi 7 H.A. Abdelrahman 8 L Al-Gazali 8 Anju Shukla, MD 9 Katta Girisha, MD 9 Masoud Garshasbi 10 Yousef Housawi 11 Fuad Al Mutairi 5 Nouriya Al-Sannaa 12 Majid Alfadhel, MD 5 Oliver Brandau, MD 1 Prof. Arndt Rolfs, MD 1, 13 Prof. Peter Bauer, MD 1
1 CENTOGENE AG 2 Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia 3 Kuwait Medical Genetics Center 4 Genatak Center for Genomic Medicine, Kuwait City, Kuwait 5 King Abdullah International Medical Research Center (KAIMRC), Riyadh 6 Sultan Qaboos University Hospital, Muscat, Oman 7 Tawam Hospital Al Ain 8 United Arab Emirates University Al Ain 9 Manipal University 10 Tarbiat Modares University, DeNA Laboratory, Tehran, Iran 11 King Fahad Specialist Hospital, Dammam, Saudi Arabia 12 John Hopkins Aramco Health Care 13 University of Rostock
June 21, 2018

These findings were presented at the annual European Human Genetics Conference (ESHG) 2018.

Validation of gene causality for neurological disorders by WES/WGS analyses in a diagnostic setting

Figure 1: Novel pedigrees as identified in our proprietary database CentoMD® for the indicated recessive disease genes

Figure 2: To-scale schemes of coding sequences (exon boundaries as stippled lines), critical protein domains, and pathogenic variants identified previously (black) and in CentoMD® (red)

Table 1: Origins of patients

GenePreviously described patients Patients from CentoMD ® (bold=novel)
NUDT2 Saudi Arabia Saudi Arabia
NKX6-2 India; Kenya/Tanzania; Morocco; Saudi Arabia Kuwait; Oman; Saudi Arabia; United Arab Emirates
GTPBP2 Iran Kuwait; Saudi Arabia
ACER3 Israel India; Saudi Arabia

Table 2: Phenotypic features

GeneDescribed previously Novel in CentoMD®-listed patients
NUDT2 Intellectual disability Low birth weight and height, muscular hypotonia, delayed motor and language development
NKX6-2 Hypomyelinating dystrophy, spastic ataxia Mild dysmorphism, seizures, clinical regression
GTPBP2 Dystonia, ataxia, cognitive dysfunction; motor neuropathy, retinal abnormalities, sparse hair, brain iron accumulation Skeletal anomalies, extra-neurological presentations, lack of clinical progression, no evidence for brain iron accumulation
ACER3 Progressive leukodystrophy (truncal hypotonia, appendicular spasticity, dystonia), short stature, late onset macrocephaly, facial dysmorphism Underweight, lactic acidosis; delayed myelination; brain atrophy

Table 3: Summary of novelties as extracted from CentoMD®