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BMC Med Genet. 2015 Jun 25;16:41. doi: 10.1186/s12881-015-0183-0.

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

Author information

1
Molecular Neuropsychiatry & Development Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. arshadrafiq68@gmail.com.
2
Currently at: Department of Physiology and Experimental Medicine (PEM), Hospital for Sick Children, Toronto, ON, Canada. arshadrafiq68@gmail.com.
3
CHUM Research Center - Notre Dame Hospital, Montreal, Canada. claire.leblond2@mail.mcgill.ca.
4
Currently at: Montreal Neurological Institute, McGill University, Montreal, QC, Canada. claire.leblond2@mail.mcgill.ca.
5
Department of Biochemistry, Quaid-I-Azam University, and Pakistan Medical Research Council, Islamabad, Pakistan. arif289@gmail.com.
6
Molecular Neuropsychiatry & Development Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. akshita.vincent@sickkids.ca.
7
CHUM Research Center - Notre Dame Hospital, Montreal, Canada. amirthagowri.ambalavanan@mail.mcgill.ca.
8
Currently at: Montreal Neurological Institute, McGill University, Montreal, QC, Canada. amirthagowri.ambalavanan@mail.mcgill.ca.
9
Department of Biochemistry, Quaid-I-Azam University, and Pakistan Medical Research Council, Islamabad, Pakistan. falakmahmand@gmail.com.
10
The Lahore Institute for Research and Development, Lahore, Punjab, Pakistan. ayyazmalik292@gmail.com.
11
University of Education, Township Campus, College Road, Lahore, Punjab, Pakistan. naseema902000@yahoo.com.
12
CHUM Research Center - Notre Dame Hospital, Montreal, Canada. dan.spiegelman@mcgill.ca.
13
Currently at: Montreal Neurological Institute, McGill University, Montreal, QC, Canada. dan.spiegelman@mcgill.ca.
14
Department of Biotechnology, University of Azad Jammu and Kashmir, P.O. Box 13100, Muzaffarabad, Pakistan. ali.phd.qau@gmail.com.
15
Dept: zoology, University of Education, Lahore, Campus Dera Ghazi Khan, Punjab, Pakistan. amin1158@hotmail.com.
16
CHUM Research Center - Notre Dame Hospital, Montreal, Canada. sandra.laurent2@mcgill.ca.
17
Currently at: Montreal Neurological Institute, McGill University, Montreal, QC, Canada. sandra.laurent2@mcgill.ca.
18
Molecular Neuropsychiatry & Development Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. huda.mahmood@mail.utoronto.ca.
19
CHUM Research Center - Notre Dame Hospital, Montreal, Canada. mehtabsindhi@yahoo.com.
20
Department of Biochemistry, Quaid-I-Azam University, and Pakistan Medical Research Council, Islamabad, Pakistan. nadiralikerio@yahoo.com.
21
Molecular Neuropsychiatry & Development Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. afennell@gmail.com.
22
Ma Ayesha Memorial Centre, Karachi, Pakistan. zohair.nanjiani@aku.edu.
23
Molecular Neuropsychiatry & Development Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. geraldegger2@gmail.com.
24
Institute of Human Genetics, Medical University of Graz, Graz, A-8010, Austria. geraldegger2@gmail.com.
25
Hôpital Rivière-des-Prairies, Montreal, Canada. chantal.crn@gmail.com.
26
Département de Psychiatrie, Université de Montréal, Montreal, Canada. chantal.crn@gmail.com.
27
Department of Biochemistry, Quaid-I-Azam University, and Pakistan Medical Research Council, Islamabad, Pakistan. waqas.ravian.ahmed@gmail.com.
28
The Lahore Institute for Research and Development, Lahore, Punjab, Pakistan. ma84@queensu.ca.
29
Division of Developmental Disabilities, Department of Psychiatry, Queen's University, Kingston, ON, Canada. ma84@queensu.ca.
30
Autism Institute, Karachi, Pakistan. autismaid1@yahoo.com.
31
Hôpital Rivière-des-Prairies, Montreal, Canada. dismaid1@yahoo.comil.
32
Département de Psychiatrie, Université de Montréal, Montreal, Canada. dismaid1@yahoo.comil.
33
Research Centre, Montreal Mental Health University Institute, 7331, rue Hochelaga, Montréal, QC, H1N 3 V2, Canada. dismaid1@yahoo.comil.
34
Département de Psychiatrie, Université de Montréal, Montreal, Canada. amelie.johnson@umontreal.ca.
35
Research Centre, Montreal Mental Health University Institute, 7331, rue Hochelaga, Montréal, QC, H1N 3 V2, Canada. amelie.johnson@umontreal.ca.
36
The Fred A. Litwin Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, Toronto, Canada. joyce.so@utoronto.ca.
37
The Centre for Addiction and Mental Health, Toronto, Canada. joyce.so@utoronto.ca.
38
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. joyce.so@utoronto.ca.
39
Sir Cowasji Jehangir Institute of Psychiatry, Hyderabad, Sindh, Pakistan. qbrohi@gmail.com.
40
Hôpital Rivière-des-Prairies, Montreal, Canada. laurent.mottron@umontreal.ca.
41
Département de Psychiatrie, Université de Montréal, Montreal, Canada. laurent.mottron@umontreal.ca.
42
Research Centre, Montreal Mental Health University Institute, 7331, rue Hochelaga, Montréal, QC, H1N 3 V2, Canada. laurent.mottron@umontreal.ca.
43
Department of Biochemistry, Quaid-I-Azam University, and Pakistan Medical Research Council, Islamabad, Pakistan. mansar_76@yahoo.com.
44
Molecular Neuropsychiatry & Development Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. john.vincent@camh.ca.
45
Department of Psychiatry, University of Toronto, Toronto, ON, Canada. john.vincent@camh.ca.
46
CHUM Research Center - Notre Dame Hospital, Montreal, Canada. lan.xiong@umontreal.ca.
47
Département de Psychiatrie, Université de Montréal, Montreal, Canada. lan.xiong@umontreal.ca.
48
Research Centre, Montreal Mental Health University Institute, 7331, rue Hochelaga, Montréal, QC, H1N 3 V2, Canada. lan.xiong@umontreal.ca.

Abstract

BACKGROUND:

Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits.

METHODS:

Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations.

RESULTS:

We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population.

CONCLUSION:

We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup.

PMID:
26104215
PMCID:
PMC4631108
DOI:
10.1186/s12881-015-0183-0
[Indexed for MEDLINE]
Free PMC Article

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