A novel homozygous nonsense NDNF variant in Kallmann syndrome

KOTAN L. D., Yildiz M., TURAN İ., CELİLOĞLU C., YÜKSEL B., Topaloglu A. K.

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, vol.191, no.3, pp.831-834, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 191 Issue: 3
  • Publication Date: 2023
  • Doi Number: 10.1002/ajmg.a.63066
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
  • Page Numbers: pp.831-834
  • Keywords: GnRH neurons, Kallmann syndrome, NDNF
  • Istanbul University Affiliated: No


Kallmann syndrome (KS) is a rare genetic disease characterized by pubertal failure and olfactory defects. Although many genes associated with KS have been reported, most are rare. Recently, heterozygous inactivating mutations in the neuron-derived neurotrophic factor gene (NDNF) were reported to cause KS. Here, we present a 14-year-old Kurdish boy with KS who has a novel homozygous nonsense c.1251C>A (p.Tyr417Ter) variant in NDNF. The variant was not observed in reference population databases and was predicted to be deleterious. Segregation analysis performed with Sanger sequencing indicated the autosomal recessive inheritance of the clinical phenotype. His heterozygous parents have experienced timely pubertal development and normal reproductive features. This study reported the first homozygous truncating NDNF variant, enabling the direct observation of the clinical consequences of predictively absent NDNF function. These results support the contention that the inactivating mutations in NDNF cause KS, and provide additional evidence for the complex inheritance of KS.