Is Whole Exome Sequencing (WES) Sufficient to Elucidate the Genetic Aetiology of Primary Enuresis Nocturna: The First Molecular-Based Large Family Study and a Brief Literature Review Tüm Ekzom Dizileme (WES), Primer Enürezis Nokturna’nın Genetik Etiyolojisini Aydınlatmak için Yeterli Midir: İlk Moleküler Temelli Geniş Aile Çalışması ve Kısa Bir Literatür Derlemesi

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Gümüş A. A., ÇAM F. S.

Turkish Journal of Child and Adolescent Mental Health, cilt.33, sa.2, ss.141-151, 2026 (Scopus)

Özet

Objectives: Enuresis nocturna is a condition that negatively affects quality of life in childhood and adulthood. Primary enuresis nocturna (PEN) is a condition in which bedwetting continues after the age of five without a dry period. PEN is called non-monosymptomatic (PNMEN) when lower urinary tract findings are present and monosymptomatic (PMEN) when they are absent. Studies on the etiology of PEN, the 4p, 8q, 12q, 13q, 22q chromosomal regions, GNAZ, DRD5, D1B, NOS1, DRD4, PRDM13, SIM1, EDNRB, AQP2 genes, rs9376454, rs60721117 variants have been proposed as genetic responsible. Here, it is aimed to clarify the genetics of enuresis by analysing the sociodemographic and genetic findings of a large family with PEN. Materials and Methods: Detailed anamnesis of the family was taken, physical examinations, ultrasonography, voiding cystourography were examined and enuresis was subtyped. Whole exome sequencing was performed in six individuals with familial segregation, the variants found in these individuals were screened in seven other individuals with PEN. Results: In our family, PEN was inherited in an autosomal dominant pattern. Six individuals had PMEN, seven individuals had PNMEN. Bladder dysfunction was in three individuals, sleep disorder was in all individuals. Common variants were found in PIGQ, CLCNKB, NCOR1, MROH2A, CCDC140 genes which may be candidates in the first group, only the c.568_571delinsTGAA (p.Arg190_Glu191delinsTer) variant in NCOR1 gene was found to be heterozygous in other family members. Conclusion: When the sociodemographic characteristics of the family were examined, bladder dysfunction and sleep disorder are the main predisposing factors for PEN. Familial PEN cases are rare and whole exome and genome studies to investigate the molecular basis of multifactorial diseases such as PEN are rarely performed. In order to clarify candidate genes in whole genome and exome studies of new PEN cases, it would be a more effective method to perform whole genome or exome studies on independent familial PEN cases.