Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Jin-Ho Choi x
Clear All Modify Search
Ja Hye Kim Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Ja Hye Kim in
Google Scholar
PubMed
Close
,
Yunha Choi Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Yunha Choi in
Google Scholar
PubMed
Close
,
Soojin Hwang Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Soojin Hwang in
Google Scholar
PubMed
Close
,
Gu-Hwan Kim Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Gu-Hwan Kim in
Google Scholar
PubMed
Close
,
Han-Wook Yoo Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Han-Wook Yoo in
Google Scholar
PubMed
Close
, and
Jin-Ho Choi Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Jin-Ho Choi in
Google Scholar
PubMed
Close

Objective

Heterozygous CHD7 mutations cause a broad spectrum of clinical phenotypes ranging from typical CHARGE syndrome to self-limited delayed puberty. This study aimed to investigate the clinical characteristics of endocrine dysfunction in patients with CHD7 mutations.

Methods

The clinical features and endocrine findings from 30 patients with CHD7 variants were retrospectively reviewed. A diagnosis of CHARGE syndrome was based on the Verloes diagnostic criteria.

Results

Seventeen patients fulfilled the criteria for typical CHARGE syndrome, one patient for partial/incomplete CHARGE, and the remaining eleven patients had atypical CHARGE syndrome. One patient was diagnosed with Kallmann syndrome and unilateral deafness. The most frequently observed features were inner ear anomalies (80.0%), intellectual disability (76.7%), and external ear anomalies (73.3%). The mean height and weight SDSs at diagnosis were −2.6 ± 1.3 and −2.2 ± 1.8, respectively. Short stature was apparent in 18 patients (60%), and 1 patient was diagnosed with growth hormone deficiency. Seventeen males showed genital hypoplasia, including micropenis, cryptorchidism, or both. Seven patients after pubertal age had hypogonadotropic hypogonadism with hyposmia/anosmia and olfactory bulb hypoplasia. Truncating CHD7 mutations were the most common (n  = 22), followed by missense variants (n  = 3), splice-site variants (n  = 2), and large deletion (n  = 2).

Conclusions

A diverse phenotypic spectrum was observed in patients with CHD7 variants, and endocrine defects such as short stature and delayed puberty occurred in most patients. Endocrine evaluation, especially for growth and pubertal impairment, should be performed during diagnosis and follow-up to improve the patient’s quality of life.

Open access
Ja Hye Kim Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Ja Hye Kim in
Google Scholar
PubMed
Close
,
Yunha Choi Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Yunha Choi in
Google Scholar
PubMed
Close
,
Soojin Hwang Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Soojin Hwang in
Google Scholar
PubMed
Close
,
Ji-Hee Yoon Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Ji-Hee Yoon in
Google Scholar
PubMed
Close
,
Jieun Lee Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea

Search for other papers by Jieun Lee in
Google Scholar
PubMed
Close
,
Min Jae Kang Department of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea

Search for other papers by Min Jae Kang in
Google Scholar
PubMed
Close
,
Gu-Hwan Kim Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Gu-Hwan Kim in
Google Scholar
PubMed
Close
,
Han-Wook Yoo Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Han-Wook Yoo in
Google Scholar
PubMed
Close
, and
Jin-Ho Choi Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Search for other papers by Jin-Ho Choi in
Google Scholar
PubMed
Close

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 (four patients with KS, one patient with nIHH, one prepubertal boy with anosmia, and one newborn patient) from six 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.

Open access