The underlying genetic drivers of
Kallmann syndrome, a rare
genetic disorder characterized by
anosmia and
hypogonadotropic hypogonadism due to impairment in the development of olfactory axons and in the migration of
gonadotropin-releasing hormone (
GNRH)-producing neurons during embryonic development, remain largely unknown. SOX10, a key
transcription factor involved in the development of neural crest cells and established as one of the causative genes of
Waardenburg syndrome, has been shown to be a causative gene of
Kallmann syndrome. A 17-year-old male patient, who was diagnosed with
Waardenburg syndrome on the basis of a
hearing impairment and hypopigmented iris at childhood, was referred to our department because of
anosmia and
delayed puberty. As clinical examination revealed an aplastic olfactory bulb and
hypogonadotropic hypogonadism, we diagnosed him as having
Kallmann syndrome. Incidentally, we elucidated that he also presented with subclinical
hypothyroidism without evidence of
autoimmune thyroiditis. Direct sequence analysis detected a nonsense SOX10 mutation (c.373C>T, p.Glu125X) in this patient. Since this
nonsense mutation has never been published as a germline variant, the SOX10 substitution is a novel mutation that results in
Kallmann syndrome and
Waardenburg syndrome. This case substantiates the significance of SOX10 as a genetic cause of
Kallmann syndrome and
Waardenburg syndrome, which possibly share a common pathway in the development of neural crest cells.
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