Genetic diagnosis of idiopathic hypogonadotrophic hypogonadism: a new point mutation in the KAL2 gene.
Kallmann Syndrome (KS) is a genetic disease of embryonic development which is characterized by the association of hypogonadotropic hypogonadism (HH) due to a deficit of the gonadotropin-releasing hormone (GnRH) and a hypo/anosmia (including a hypoplasia of the nasal sulcus and agenesis of the olfactory bulbs). Even though it is a genotypically and phenotypically heterogeneous clinical disease, there are some key genes related to KS (KAL1, FGFR1 (KAL2), GNRHR, KISSR1 (GPR54), GNRH1, NELF and PROK2). The aim of this study was to present a case report of a genetic diagnosis of KS linked to the presence of mutations in the FGFR1 (fibroblast growth factor receptor 1, also known as KAL2) gene. This diagnosis was made in a 44-year old female affected by a hypogonadism for which she had received intermittent treatment until she was 30 years old based on the patient's own decision. The molecular analysis of FGFR1 identified the mutation c. 246_247delAG (p.T82Xfs110) in heterozygosis on exon 3 of the KAL2 gene. This is the first report of this mutation related to idiopathic hypogonadotrophic hypogonadism (IHH).
LORGEN G.P., PT, Ciencias de la Salud - BIC, Granada, Spain.
Carmen
C
Entrala-Bernal
UGC Endocrinologίa y Nutriciόn, Complejo Hospitalario de Jan, Spain.
Cristina
C
Montes-Castillo
Laboratorio de Identificaciün Gentica, Departamento de Medicina Legal y Toxicologίa, Facultad de Medicina, Universidad de Granada; Granada, Spain.
Maria Jesus
MJ
Alvarez-Cubero
UGC Endocrinologίa y Nutriciόn, Complejo Hospitalario de Jan, Spain.
Carmen
C
Gutiérrez-Alcántara
LORGEN G.P., PT, Ciencias de la Salud - BIC, Granada, Spain.
Francisco
F
Fernandez-Rosado
LORGEN G.P., PT, Ciencias de la Salud - BIC, Granada, Spain.
Esther
E
Martinez-Espίn
UGC Endocrinologίa y Nutriciόn, Complejo Hospitalario de Jan, Spain.
Carolina
C
Sánchez-Malo
UGC Endocrinologίa y Nutriciόn, Complejo Hospitalario de Jan, Spain.
Piedad
P
Santiago-Fernández
D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D017436:Kallmann Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D011237:Predictive Value of Tests; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*
C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1