c.4168G>A(p.Ala 1390Thr) Variation in KMT2D Gene Detected in an Ultra-treatment-resistant Schizophrenia Patient: A Case Report and Literature Review

• Published in: Noro psikiyatri arsivi 2023, Vol.60 (4), p.380-384
• Main Authors: Alp, Anıl, Eroğlu, Elçin Özçelik, Yıldız, M İrem, Ceylan, Ahmet Cevdet, Demir, Başaran, Özer, Suzan
• Format: Report
• Language: English
• ISSN: 1300-0667
• DOI: 10.29399/npa.28417

Schizophrenia has a multifactorial etiology with a significant genetic component. Genome-wide association studies have identified common variants in candidate genes. However, the common variant can only account for a portion of the genetic variation underlying the disorder. Therefore, researchers suggest that rare variants may be one source of missing heritability in schizophrenia. We report the case of a 20-year-old male patient diagnosed with early-onset and ultra-treatment-resistant schizophrenia and mild intellectual disability and discuss certain rare genetic variants that may be involved in the etiology. He was hospitalized for the initiation of clozapine treatment and was referred to the department of genetics because he had macrocephaly, high arched palate, a prominent forehead, hearing impairment, and hyperpigmented skin lesions. The whole exome sequencing analysis revealed a heterozygous 4168G>A(p.Ala1390Thr) variant in exon 15 of KMT2D (Lysine N-Methyltransferase 2D) (NM_003482.4) gene, which is associated with Kabuki Syndrome. The variants in KMT2D have been reported to be associated with brain development and may play a role in schizophrenia. We discussed the relationship between schizophrenia and genetic variants detected in this case in light of the literature.