Abstract
Objectives
Bipolar disorder (BPD) is a neuropsychiatric disorder with a complex pattern of inheritance. Although many genetic studies have been conducted on BPD, 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 BPD 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 BPD in this family. Further analysis of these two genes in BPD patients and functional evaluation of the allelic variants identified are suggested.