full clinical features of CHARGE syndrome. CHD7 variants have been identified in normosmic isolated hypogonadotropic hypogonadism (nIHH), Kallmann syndrome (KS), self-limited delayed puberty, as well as CHARGE syndrome ( 3 , 4 , 5 , 6 , 7
Ja Hye Kim, Yunha Choi, Soojin Hwang, Gu-Hwan Kim, Han-Wook Yoo, and Jin-Ho Choi
Rui-yi Tang, Rong Chen, Miao Ma, Shou-qing Lin, Yi-wen Zhang, and Ya-ping Wang
, including deafness, renal abnormalities and digital anomalies ( 1 , 2 ). Furthermore, IHH can be categorized according to olfactory function as IHH with a normal sense of smell (normosmic IHH; nIHH) and IHH with anosmia/hyposmia (Kallmann syndrome; KS
Ja Hye Kim, Yunha Choi, Soojin Hwang, Ji-Hee Yoon, Jieun Lee, Min Jae Kang, Gu-Hwan Kim, Han-Wook Yoo, and Jin-Ho Choi
Objective: This study was performed to investigate the molecular characteristics and frequency of copy number variations (CNVs) of ANOS1 in patients with Kallmann syndrome (KS) or normosmic isolated hypogonadotropic hypogonadism (nIHH) using multiplex ligation-dependent probe amplification (MLPA) analysis and sequencing.
Methods: Among 45 patients from 43 independent families, Sanger sequencing, next-generation sequencing (NGS), or microarray was performed in 24 patients from 23 families, and MLPA was performed in 19 patients who did not show rare sequence variants (n = 18) or ANOS1 amplification by PCR (n = 1).
Results: Seven patients (4 patients with KS, 1 patient with nIHH, one prepubertal boy with anosmia, and one newborn patient) from 6 families (6/43, 14%) harbored molecular defects in ANOS1 including a nonsense mutation [c.1140G>A (p.W380*)], a frameshift mutation [c.1260del (p.Q421Kfs*61)], a splice site mutation (c.1449+1G>A), an exon 7 deletion, a complete deletion, and 7.9 Mb-sized inversion encompassing ANOS1. The complete deletion of ANOS1 was identified in a neonate with a micropenis and cryptorchidism. Unilateral renal agenesis was found in three patients, whereas only one patient displayed both synkinesia and sensorineural hearing loss. There was no reversal of hypogonadotropic hypogonadism in any patient during 9.1 ± 2.9 years of treatment with testosterone enanthate.
Conclusions: Molecular defects in the ANOS1 gene could be identified in 14% of probands including various types of CNVs (3/43, 7.0%). Comprehensive analysis using sequencing and analysis for CNVs is required to detect molecular defects in ANOS1.
Anna-Pauliina Iivonen, Johanna Känsäkoski, Kirsi Vaaralahti, and Taneli Raivio
hypogonadotropic hypogonadism is called normosmic (ncHH) if patients have normal sense of smell, whereas Kallmann syndrome (KS) is a form of the same disease where patients have absent or deficient smell ( 2 ). In the case of normosmic cHH, abnormal GnRH function
Shota Dzemaili, Jitske Tiemensma, Richard Quinton, Nelly Pitteloud, Diane Morin, and Andrew A Dwyer
. Living with Kallmann syndrome – analysis of subjective experience reports from women . Geburtshilfe Frauenheilkd 2013 73 1112 – 1120 . ( doi:10.1055/s-0033-1350881 ) 31 DiMatteo MR Lepper HS Croghan TW. Depression is a risk factor
Catarina I Gonçalves, José M Aragüés, Margarida Bastos, Luísa Barros, Nuno Vicente, Davide Carvalho, and Manuel C Lemos
hormone deficiencies. CHH may occur associated with anosmia, a condition referred as Kallmann syndrome, or may occur without associated olfactory abnormalities, referred to as normosmic CHH (nCHH) ( 1 ). Genetic studies of patients with CHH have identified
Fernanda A Correa, Ericka B Trarbach, Cintia Tusset, Ana Claudia Latronico, Luciana R Montenegro, Luciani R Carvalho, Marcela M Franca, Aline P Otto, Everlayny F Costalonga, Vinicius N Brito, Ana Paula Abreu, Mirian Y Nishi, Alexander A L Jorge, Ivo J P Arnhold, Yisrael Sidis, Nelly Pitteloud, and Berenice B Mendonca
/or Kallmann syndrome (KS), such as midline cerebral and facial defects (3) . The adenohypophyseal and olfactory placodes share a common embryological origin as they both emerge from the preplacodal field, which could explain this overlap (4) . FGFR1, a
M I Stamou, P Varnavas, L Plummer, V Koika, and N A Georgopoulos
heterogeneous IGD only ~50% of patients have a genetic mutation that is identifiable ( 2 , 6 ). Mutations in genes that disrupt the neurodevelopmental pathway of GnRH, that is the development and migration of GnRH neurons cause Kallmann Syndrome (KS), and
Agnieszka Pazderska, Yaasir Mamoojee, Satish Artham, Margaret Miller, Stephen G Ball, Tim Cheetham, and Richard Quinton
://doi.org/10.1111/cen.13236 ) 27647266 10.1111/cen.13236 6 Smith N Quinton R. Kallmann syndrome . BMJ 2012 345 e6971 . ( https://doi.org/10.1136/bmj.e6971 ) 10.1136/bmj.e6971 23207501 7 Howard S Dunkel L. Sex steroid and
Kristian Almstrup, Hanne Frederiksen, Anna-Maria Andersson, and Anders Juul
transporter, highly expressed in liver SLC45A4 Σphth.m Σphth.m Σphth.m No Involved in cognitive functions (51) SOX10 Σphth.m Σphth.m Σphth.m Yes Involved in Kallmann syndrome (52) and hypogonadotropic hypogonadism (53