OBJECTIVE: To investigate the inheritance pattern of two missense PROKR2 changes within a single family. DESIGN: This is a descriptive study. SETTING: Tertiary referral center. PATIENT(S): The proband and his brother, both with congenital hypogonadotropic hypogonadism and anosmia (Kallmann syndrome). INTERVENTION(S): Clinical and biochemical evaluation of Kallmann syndrome. Sequence analysis of the coding exons and exon-intron boundaries of KAL1, FGFR1, FGF8, PROK2, and PROKR2 from polymerase chain reaction (PCR)-amplified genomic DNA. Recombinant human FSH treatment of the proband. MAIN OUTCOME MEASURE(S): Phenotypic and genotypic features, and inhibin B response to recombinant human FSH. RESULT(S): The proband and his brother were homozygous for two variants in PROKR2; a novel mutation c.701G>A (p.G234D), and a polymorphism c.802C>T (p.R268C). Recombinant human FSH therapy of the proband increased serum inhibin B from <16 to 136 ng/L. The heterozygous parents were fertile and had six children. CONCLUSION(S): These findings are consistent with recessive mode of inheritance. PROKR2 signaling does not directly affect Sertoli cell function.
OBJECTIVE: To investigate the inheritance pattern of two missense PROKR2 changes within a single family. DESIGN: This is a descriptive study. SETTING: Tertiary referral center. PATIENT(S): The proband and his brother, both with congenital hypogonadotropic hypogonadism and anosmia (Kallmann syndrome). INTERVENTION(S): Clinical and biochemical evaluation of Kallmann syndrome. Sequence analysis of the coding exons and exon-intron boundaries of KAL1, FGFR1, FGF8, PROK2, and PROKR2 from polymerase chain reaction (PCR)-amplified genomic DNA. Recombinant human FSH treatment of the proband. MAIN OUTCOME MEASURE(S): Phenotypic and genotypic features, and inhibin B response to recombinant human FSH. RESULT(S): The proband and his brother were homozygous for two variants in PROKR2; a novel mutation c.701G>A (p.G234D), and a polymorphism c.802C>T (p.R268C). Recombinant human FSH therapy of the proband increased serum inhibin B from <16 to 136 ng/L. The heterozygous parents were fertile and had six children. CONCLUSION(S): These findings are consistent with recessive mode of inheritance. PROKR2 signaling does not directly affect Sertoli cell function.
Authors: Kimberly H Cox; Luciana M B Oliveira; Lacey Plummer; Braden Corbin; Thomas Gardella; Ravikumar Balasubramanian; William F Crowley Journal: Hum Mol Genet Date: 2018-01-15 Impact factor: 6.150