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.
Bipolar Disord. 2020 Feb;22(1):70-78. doi: 10.1111/bdi.12815. Epub 2019 Aug 21.
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.
We analysed a four-generation family with several of its members diagnosed for BD employing a combination of genetic linkage and exome analysis.
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.
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.
双相情感障碍（BD）是一种具有复杂遗传模式的神经精神疾病。尽管已经对 BD 进行了许多遗传研究，但它的遗传相关性仍不确定。本研究旨在确定一个经过全面临床评估和随访超过 12 年的印度家族中该疾病的遗传基础。
我们分析了一个有几代人的家族，其中一些成员被诊断为 BD，采用了遗传连锁和外显子分析的组合。
我们获得了染色体 1 和染色体 6 标记（D1S410；LOD=3.01，Ө=0；和 D6S289；LOD=1.58，Ө=0）的提示性 LOD 分数。对包含这两个标记的区域进行手动单体型分析有助于限定一个关键的基因组间隔 32.44 Mb（D1S2700-D1S435；染色体 1p31.1-13.2）和另一个 10.34 Mb（D6S470-D6S422；染色体 6p22.3-22.2）。我们检查了对应于这两个区间的外显子序列，发现了罕见的变体 NM_181712.4：c.2461G>T（p.Asp821Tyr）在 1p31.1-13.2 中的 KANK4；和 NM_006366：c.-93G>A，在 6p22.3-22.2 中的 CAP2 的 5'UTR 中。
我们的研究表明 KANK4 或 CAP2 或两者都参与了这个家族的 BD。建议在 BD 患者中进一步分析这两个基因，并对鉴定出的等位变体进行功能评估。
