TY - JOUR
T1 - Molecular genetic and clinical delineation of 22 patients with congenital hypogonadotropic hypogonadism
AU - Aoyama, Kohei
AU - Mizuno, Haruo
AU - Tanaka, Tatsushi
AU - Togawa, Takao
AU - Negishi, Yutaka
AU - Ohashi, Kei
AU - Hori, Ikumi
AU - Izawa, Masako
AU - Hamajima, Takashi
AU - Saitoh, Shinji
N1 - Publisher Copyright:
© 2017 2017 Walter de Gruyter GmbH, Berlin/Boston.
PY - 2017/10/26
Y1 - 2017/10/26
N2 - Congenital hypogonadotropic hypogonadism (CHH) is classified as Kallmann syndrome (KS) with anosmia/hyposmia or normosmic (n)CHH. Here, we investigated the genetic causes and phenotype-genotype correlations in Japanese patients with CHH. We enrolled 22 Japanese patients with CHH from 21 families (18 patients with KS and 4 with nCHH) and analyzed 27 genes implicated in CHH by next-generation and Sanger sequencing. We detected 12 potentially pathogenic mutations in 11 families, with three having a mutation in ANOS1 (X-linked recessive); three and four having a mutation in FGFR1 and CHD7, respectively (autosomal dominant); and one having two TACR3 mutations (autosomal recessive). Among four patients with KS carrying a CHD7 mutation, one had perceptive deafness and two had a cleft lip/palate. The frequency of CHH genes in the Japanese was compatible with previous reports, except that CHD7 mutations might be more common. Furthermore, partial phenotype-genotype correlations were demonstrated in our cohort.
AB - Congenital hypogonadotropic hypogonadism (CHH) is classified as Kallmann syndrome (KS) with anosmia/hyposmia or normosmic (n)CHH. Here, we investigated the genetic causes and phenotype-genotype correlations in Japanese patients with CHH. We enrolled 22 Japanese patients with CHH from 21 families (18 patients with KS and 4 with nCHH) and analyzed 27 genes implicated in CHH by next-generation and Sanger sequencing. We detected 12 potentially pathogenic mutations in 11 families, with three having a mutation in ANOS1 (X-linked recessive); three and four having a mutation in FGFR1 and CHD7, respectively (autosomal dominant); and one having two TACR3 mutations (autosomal recessive). Among four patients with KS carrying a CHD7 mutation, one had perceptive deafness and two had a cleft lip/palate. The frequency of CHH genes in the Japanese was compatible with previous reports, except that CHD7 mutations might be more common. Furthermore, partial phenotype-genotype correlations were demonstrated in our cohort.
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U2 - 10.1515/jpem-2017-0035
DO - 10.1515/jpem-2017-0035
M3 - Article
C2 - 28915117
AN - SCOPUS:85031012217
SN - 0334-018X
VL - 30
SP - 1111
EP - 1118
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
IS - 10
ER -