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

• DOI: 10.1186/s12881-015-0183-0
• Publication Date: 2015-06-24T02:33:47Z
• Authors: Muhammad Arshad R...; Claire S Leblond; Muhammad Arif Nad...; Akshita K. Vincent; Amirthagowri Amba...; Falak Sher Khan; Muhammad Ayaz; Naseema Shaheen; Dan Spiegelman; Ghazanfar Ali; Muhammad Amin-ud-din; Sandra Laurent; Huda Mahmood; Mehtab Christian; Nadir Ali; Alanna Fennell; Zohair Nanjiani; Gerald Egger; Chantal Caron; Ahmed Waqas; Muhammad Ayub; Saima Rasheed; Baudouin Forgeot ...; Amelie Johnson; Joyce So; Muhammad Qasim Brohi; Laurent Mottron; Muhammad Ansar; John B Vincent; Lan Xiong
• Keywords: Sanger sequencing; Human genetics; Disease gene identification; Founder effect; Runs of Homozygosity

Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We three large consanguineous Pakistani families with intellectual disability in some cases autistic traits.Clinical assessments were performed order to allow comparison of clinical features other VPS13B mutations. Homozygosity mapping followed whole exome sequencing Sanger strategies used identify disease-related mutations.We two novel homozygous deletion mutations VPS13B, firstly 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, secondly exons 37-40, which co-segregate affected status. In addition COH1-related traits, reported number family members, contrasting the "friendly" demeanour often associated COH1. The c.6879delT mutation present from different regions country, but both Baloch sub-ethnic group, shared haplotype, indicating founder effect among population.We suspect that may be common cause COH1 similar phenotypes population. Additionally, most individuals these also like suggests this variant lead distinct autistic-like subgroup.