Clinical Research Details

Descriptive Information
Genome Sequencing to Elucidate the Causes and Mechanisms of Mendelian Genetic Disorders

Ziad Nahas


Clinical Research - Mechanisms of Human Disease  

Mark Doumit
Extension: 5666
Conditions and Keywords
Mendelian Disorders
Mendelian Disorders,Genetic Sequencing
Study Design
N/A: Not Applicable
N/A: Not Applicable
N/A: Not Applicable
N/A: Not Applicable
Eligibility and IRB
Min: 13
Max: 90
In Progress

If a genetic mutation is passed on in a family and causes disease in a discrete, observable pattern, then this disease is termed a Mendelian disorder. The cause of many Mendelian genetic diseases is known; however, there are thousands for which the cause is not known. The aim of this project is to investigate the genetic causes of Mendelian diseases through genome and exome sequencing. In particular, this study aims to identify those Mendelian genetic diseases that are expressed or apparent but have no identified associated gene, or are associated or expressed through several genes, and/or new Mendelian diseases with an unknown diagnosis. This approach had been taken before to identify genetic causes of autism, Parkinson’s disease, oncogenesis, diabetes, schizophrenia, and ADHD (Amir et al., 1999; Fujioka et al., 2014; Piven et al., 2013; Atkinson et al., 2001; Bergholdt et al., 2007; Lam et al., 2006; Pociot et al., 2004). Objective: Overall, our goal is to identify the genes responsible for ≈9,000 Mendelian disorders.  Any new or returning patients from AUBMC inpatient or outpatient setting will be reviewed for acceptance into the research pipeline. Preferably, the participants being reviewed for acceptance should have a disease or illness that is shared with or similar to individuals in their family from older and/or younger generations. Hypothesis: This would also allow us to investigate the heritability of the disease and possibly control for those diseases associated or expressed through several genes. Method: Biological samples (blood, saliva, or buccal brushing) will be collected at AUBMC. A portion of the samples will then be frozen and shipped to our collaborators at BCM for genetic testing; another portion will be stored at AUBMC in the DTS building for similar procedures. High throughput DNA sequencing technology will be used in conjunction with exome and genome sequencing. By investigating the genetic commonalities of participants with the same or similar diseases we are able to identify, isolate, change, “knock-out”, and/or further investigate the phenotypic homologue of that gene. This bottom-up approach should eventually provide targeted, purposeful, and guided treatment and/or resolution to these diseases as opposed to the current status of symptom amelioration, incidentally discovered medications, and unknown diagnoses.   

The population we will be recruiting from will be from the American University of Beirut Medical Center Psychiatry Department. Patients that qualify for being included in the study will be contacted and consented; they will also be asked to contact members of their family with neuropsychiatric disorders as well as healthy family members in order to draw more definitive conclusions about the heritability of certain genes.

A physician at the AUBMC Psychiatry Department will refer study personnel to the prospective participant (a patient at the department). Study personnel will recruit and consent the participant and ask for them to ask family members about their willingness to participate as well as provide those family members with the personnel's contact information.

Families with more than one individual with a neuropsychiatric disease will be prioritized over healthy families or those with only one person with a neuropsychiatric disease. This is to better investigate the genetic links between these diseases and their heritability throughout the pedigree.

Inclusion criteria include adult individuals and children with disease of suspected genetic origin and their family members. In particular those who have a, (a) Known Mendelian phenotype with no gene identified, (b) Known Mendelian phenotype with genetic locus heterogeneity, (c) New Mendelian phenotype with unknown diagnosis that is consistent and segregates in a Mendelian fashion.