A linkage and exome study implicates rare variants of KANK4 and CAP2 in bipolar disorder in a multiplex family.

Autor: Anjanappa RM; Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India., Nayak S; Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India., Moily NS; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India., Manduva V; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India., Nadella RK; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India., Viswanath B; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India., Reddy YCJ; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India., Jain S; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India., Anand A; Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.; Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Jazyk: angličtina
Zdroj: Bipolar disorders [Bipolar Disord] 2020 Feb; Vol. 22 (1), pp. 70-78. Date of Electronic Publication: 2019 Aug 21.
DOI: 10.1111/bdi.12815
Abstrakt: Objectives: Bipolar disorder (BD) is a neuropsychiatric disorder with a complex pattern of inheritance. Although many genetic studies have been conducted on BD, its genetic correlates remain uncertain. This study was aimed at  identifying the genetic underpinnings of the disorder in an Indian family, which has been under comprehensive clinical evaluation and follow-up for over 12 years.
Methods: We analysed a four-generation family with several of its members diagnosed for BD employing a combination of genetic linkage and exome analysis.
Results: We obtained suggestive LOD score for a chromosome 1 and a chromosome 6 marker (D1S410; LOD = 3.01, Ө = 0; and D6S289; LOD = 1.58, Ө = 0). Manual haplotyping of the regions encompassing these two markers helped delimit a critical genomic interval of 32.44 Mb (D1S2700-D1S435; chromosome 1p31.1-13.2) and another of 10.34 Mb (D6S470-D6S422; chromosome 6p22.3-22.2). We examined the exomic sequences corresponding to these two intervals and found rare variants, NM_181712.4: c.2461G>T (p.Asp821Tyr) in KANK4 at 1p31.1-13.2; and NM_006366:c.-93G>A, in the 5' UTR of CAP2 at 6p22.3-22.2.
Conclusions: Our studysuggests involvement of KANK4 or CAP2 or both in BD in this family. Further analysis of these two genes in BD patients and functional evaluation of the allelic variants identified are suggested.
(© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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