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Orphanet J Rare Dis. 2019 Jun 14;14(1):144. doi: 10.1186/s13023-019-1111-8.

Novel genotypes and phenotypes among Chinese patients with Floating-Harbor syndrome.

Author information

1
Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, People's Republic of China.
2
Department of Genetics and Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, People's Republic of China.
3
Dongguan Maternal and Child Health Care Hospital, Dongguan, 523120, People's Republic of China.
4
Department of pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.
5
Department of Endocrinology, Metabolism, and Genetics, Jiangxi Provincial Children's Hospital, Nanchang, 330006, People's Republic of China.
6
Department of Pediatrics Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, People's Republic of China.
7
Department of Endocrinology, Genetics and Metabolism, Xi'an Children's Hospital Affiliated with the School of Medicine, Xi'an Jiaotong University, Xi'an, 710000, People's Republic of China.
8
Department of Pediatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
9
Department of Pediatrics, The Peoples Hospital of The Guizhou Province, Guiyang, 550002, People's Republic of China.
10
Department of Endocrinology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.
11
Department of pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China. 13333015983@163.com.
12
Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, People's Republic of China. yiping.shen@childrens.harvard.edu.
13
Department of Genetics and Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, People's Republic of China. yiping.shen@childrens.harvard.edu.
14
Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA. yiping.shen@childrens.harvard.edu.

Abstract

BACKGROUND:

Floating-Harbor syndrome (FHS) is a rare syndromic short stature disorder caused by truncating variants in SRCAP. Few Chinese FHS patients had been reported so far and limited knowledge regarding the benefit of growth hormone treatment existed.

METHODS:

We ascertained 12 short stature patients with molecularly confirmed diagnosis of FHS by whole exome sequencing. We performed a comprehensive clinical evaluation for all patients and assessed the responsiveness of growth hormone treatment in a subset of the patients.

RESULTS:

Five distinct pathogenic/likely pathogenic variants were identified in 12 independent FHS patients including two previously reported variants (c.7303C > T/p.Arg2435Ter and c.7330C > T/p.Arg2444Ter) and three novel variants (c.7189G > T/p.Glu2397Ter, c.7245_7246delAT/p.Ser2416ArgfsTer26 and c.7466C > G/p.Ser2489Ter). The c.7303C > T/p.Arg2435Ter mutation appears more common in Chinese FHS patients. The clinical presentations of Chinese FHS patients are very similar to those of previously reported patients of different ethnicities. Yet we noticed micropenis and ear abnormalities in multiple patients, suggesting that these may be novel phenotypes of Floating-Harbor syndrome. Eight patients (one with GH deficiency, one with undetermined GH level, six without GH deficiency) underwent growth hormone treatment, 3 patients had good responses, one with modest and two with poor responses.

CONCLUSION:

We described novel genotypes and phenotypes in a Chinese FHS patient cohort. We showed that about half of FHS patients exhibited modest to good response to GH treatment regardless of their respective GH deficiency status. We didn't find any correlation between different mutations and response to GH treatment.

KEYWORDS:

Chinese; Floating-Harbor syndrome; Growth hormone deficiency; SRCAP; Short stature

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