%0 Journal Article
%T Genetic Variability of SOX10-Related Disorders within an Italian Family: Straddling the Line between Kallmann and Waardenburg Syndrome.
%A Graziani L
%A Carriero ML
%A Pozzi F
%A Minotti C
%A Andreadi A
%A Bellia A
%A Ruta R
%A Bengala M
%A Novelli A
%A Lauro D
%A Novelli G
%J Mol Syndromol
%V 15
%N 4
%D 2024 Aug
%M 39119450
%F 1.494
%R 10.1159/000536574
%X <B>UNASSIGNED: </B>Kallmann syndrome (KS) is a genetically heterogeneous developmental disorder that most often manifests hypogonadotropic hypogonadism (HH) and hypo-/anosmia due to early embryonic impairment in the migration of gonadotropin-releasing hormone neurons. SOX10 (SRY-Box 10; MIM*602229), a key transcriptional activator involved in the development of neural crest cells, has been associated with KS and is identified as one of the causative genes of Waardenburg syndrome (WS).<BR><B>UNASSIGNED: </B>A 28-year-old female patient, who was clinically diagnosed with KS in her childhood, presented with HH and anosmia, mild bilateral sensorineural hearing loss (SNHL), and pigmentation abnormalities. Next-generation sequencing analysis detected a missense heterozygous SOX10 pathogenic variant (NM_006941.4:c.506C>T) in the proposita and in her mother, whose phenotype included exclusively anosmia and hypopigmented skin patches. The same variant has been described by Pingault et al. [Clin Genet. 2015;88(4):352-9] in a patient with apparently isolated bilateral severe SNHL.<BR><B>UNASSIGNED: </B>Our finding substantiates the extreme phenotypic variability of SOX10-related disorders, which range from classical KS and/or WS to contracted endophenotypes that could share a common pathway in the development of neural crest cells and highlights the need for careful evaluation and long-term follow-up of SOX10 patients, with special focus on atypical/additional and/or late-onset phenotypic traits.