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Objective To summarize the clinical and genetic characteristics of autosomal dominant disease Floating-harbor syndrome（FHS）caused by SRCAP gene mutation. Methods The clinical and genetic data of 2 patients with FHS were analyzed retrospectively. Results Two male patients were characterized by the typical facial dysmorphic features（triangular face，deep-set eyes，long eyelashes，prominent nose，short philtrum，wide and low-hanging columella， wide mouth with a slightly everted lower lip and low-set ears），short stature with significantly delayed bone age，expressive language delay，and skeletal dysplasia. Whole exome sequencing found two de novo nonsense variants in the SRCAP gene，and the mutation site of patient 1 was not reported in the literature database. The heterozygous nonsense mutation sites of both patients were located in exon 34，which were c. 7255C>T（p. q2419x，patient1）and c. 7466C>G（p. s2489x， patient2），respectively. Sanger sequencing verified that neither parent of both patients carried the mutation. The two mutations were predicted to be pathogenic based on MutationTaster and PROVEAN. Clustal Omega website analysis showed that Gln 2419 and Ser2489 in SRCAP residues were highly conserved in mammals. PubmedCD-search analysis showed that the truncation mutation of SRCAP protein caused by these two site mutations did not affect the conserved domain of the protein. According to PubmedCD-Search systerm analysis，the truncation mutation of SRCAP protein caused by these two mutations，did not affect the conserved domain of the protein，but resulted in the loss of three AT-hook domains. According to ACMG，these two variants were determined to be pathogenic. Conclusions The clinical features of two cases with FHS are dysmorphic facial features，short stature，significantly delayed bone age，delayed language development and skeletal deformities. The genetic characteristics of both patients are heterozygous nonsense mutations in SRCAP gene， which could lead to protein truncation mutations and are pathogenic. [ABSTRACT FROM AUTHOR]

Floating-Harbor syndrome is a sporadic autosomal dominantly inherited malformation syndrome characterized by typical craniofacial findings, proportional short stature, significantly delayed bone age, delayed expressive language, delayed speech, and normal head circumference. It is caused by heterozygous mutations in the SNF2-associated CBP activator protein gene (SRCAP) located on chromosome 16. Here, we report 9 years and 4 months old male patient who presented to the pediatric genetics outpatient clinic with retardation in early developmental stages, dysmorphic facial features, and short stature. The patient was diagnosed with Floating-Harbor syndrome with typical facial features and clinical findings. A triangular face, short filtrum, posteriorly rotated ear, deep-set eyes, bulbous nose, prominent columella, and low hairline are unique facial features in the syndrome. He also has short stature, significant retardation in bone age, and retardation in expressive language. Floating-Harbor syndrome should be remembered in the differential diagnosis of patients evaluated for short stature and learning disability with its unique facial features. By reporting a new case of Floating-Harbor syndrome we aimed to expand the clinical and molecular spectrum in this rare syndrome and increase diagnostic awareness for pediatric endocrinology practitioners.

Introduction: We aimed to summarize the clinical characteristics of Floating-Harbor syndrome (FHS) and the effect of recombinant human growth hormone (rhGH) to increase height.Methods: The clinical manifestations, gene sequencing results, treatment, and regression of one child with FHS were reported at the Department of Pediatrics, General Hospital of Tianjin Medical University, in July 2020. PubMed was searched using the keyword “Floating-Harbor Syndrome” up to March 2021 to obtain clinical information on children with FHS for review.Results: The child, who was a male aged 6 years and 9 months, presented to the clinic with main complaints of delayed language development since childhood and a short stature for 4 years. The child's short stature, peculiar facial features, delayed language development, and delayed bone development were considered alongside genetic testing and Sanger sequencing to verify the results. A heterozygous mutation (c.7401delC; p.Ile2468Phefs*7) was identified in exon 34 of the SRCAP gene, which was a frameshift mutation, and Sanger verification showed that neither parent had this mutation. The child was administered subcutaneous injection of rhGH (0.13 U/kg/day) and was followed up regularly. At the time of writing, the child had been treated for 6 months and was 7 years and 3 months old with a height of 106.3 cm (−3.69 SDS), which was a height increase of 6.3 cm. The patient did not complain of discomfort during treatment and presented normal laboratory tests results. Twenty-two children with FHS treated with rhGH were included in the literature review, and most of these patients demonstrated an increase in height SDS without adverse effects.Conclusion: Short stature, delayed skeletal maturation, impaired language expression, intellectual deficits, and peculiar facial features are the main clinical features of FHS. rhGH can be used as a treatment to increase height in patients with FHS, but its effectiveness and safety still need to be monitored in larger sample sizes over longer periods of time.

Floating-Harbor syndrome (FHS) is an autosomal dominant genetic disease caused by SRCAP mutation. This article reports the clinical features of a boy with FHS. The boy, aged 11 years and 7 months, attended the hospital due to short stature for more than 8 years and had the clinical manifestations of unusual facial features (triangularly shaped face, thin lips and long eyelashes), skeletal dysplasia (curvature finger), expressive language disorder, and retardation of bone age. Genetic detection revealed a novel heterozygous mutation, c.7330 C>T(p.R2444X), in the SRCAP gene. The boy was diagnosed with FHS based on these clinical manifestations and gene detection results. FHS is rare in clinical practice, which may lead to missed diagnosis and misdiagnosis, and gene detection may help with the clinical diagnosis of FHS in children. [ABSTRACT FROM AUTHOR]

Floating-Harbor syndrome is a rare autosomal dominant genetic disorder associated with SRCAP mutation. To date, approximately 50 cases of Floating-Harbor syndrome have been reported, but none have been reported in Korea yet. Floating-Harbor syndrome is characterized by delayed bony maturation, unique facial features, and language impairment. Here, we present a 6-year-old boy with a triangular face, deep-set protruding eyes, low-set ears, wide nose with narrow nasal bridge, short philtrum, long thin lips, clinodactyly, and developmental delay that was transferred to our pediatric clinic for genetic evaluation. He showed progressive delay in the area of language and cognition-adaption as he grew. He had previously undergone chromosomal analysis at another hospital due to his language delay, but his karyotype was normal. We performed targeted exome sequencing, considering several syndromes with similar phenotypes. Library preparation was performed with the TruSight One sequencing panel, which enriches the sample for about 4,800 genes of clinical relevance. Massively parallel sequencing was conducted with NextSeq. An identified variant was confirmed by Sanger sequencing of the patient and his parents. Finally, the patient was confirmed as the first Korean case of Floating-Harbor syndrome with a novel SRCAP (Snf2 related CREBBP activator protein) mutation (c.7732dupT, p.Ser2578Phefs*6), resulting in early termination of the protein; it was not found in either of his healthy parents or a control population. To our knowledge, this is the first study to describe a boy with Floating-Harbor syndrome with a novel SRCAP mutation diagnosed by targeted exome sequencing in Korea. [ABSTRACT FROM AUTHOR]

We describe a patient with speech impairment, global developmental delay, behavioural problems and a 186 kb de novo microdeletion on 16p11.2. There are four OMIM Phenotypes entries partially overlapping with the deleted region and related to recurrent microdeletions/microduplications in 16p11.2. A detailed review of published data shows that microdeletions/microduplications boundaries’ do not include genes that are deleted in the case here reported. The deletion encompasses 9 RefSeq genes and includes SRCAP (Snf2-related CREBBP activator protein, OMIM*611421), a disease causing gene. Recently, truncating mutations in the SRCAP gene have been shown to cause Floating-Harbor syndrome (FHS, OMIM#136140), a rare disorder characterized by peculiar facial features, short stature with delayed osseous maturation and speech impairment. The patient reported here shows few subtle phenotypic features resembling that of FHS, but she does not have sufficient signs and symptoms for the clinical diagnosis and a clinical classification based on facial gestalt is not possible. This is the first report of a 16p11.2 deletion completely removing one copy of SRCAP , suggesting that haploinsufficiency of this gene could be associated to speech impairment, global developmental delay, behavioural problems and few subtle phenotypic features resembling FHS. However, further evidence for the putative causative role of SRCAP isolated deletion is needed. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to summarize the clinical characteristics of Floating-Harbor syndrome (FHS) and the effect of recombinant human growth hormone (rhGH) to increase height. Methods: The clinical manifestations, gene sequencing results, treatment, and regression of one child with FHS were reported at the Department of Pediatrics, General Hospital of Tianjin Medical University, in July 2020. PubMed was searched using the keyword "Floating-Harbor Syndrome" up to March 2021 to obtain clinical information on children with FHS for review. Results: The child, who was a male aged 6 years and 9 months, presented to the clinic with main complaints of delayed language development since childhood and a short stature for 4 years. The child's short stature, peculiar facial features, delayed language development, and delayed bone development were considered alongside genetic testing and Sanger sequencing to verify the results. A heterozygous mutation (c.7401delC; p.Ile2468Phefs * 7) was identified in exon 34 of the SRCAP gene, which was a frameshift mutation, and Sanger verification showed that neither parent had this mutation. The child was administered subcutaneous injection of rhGH (0.13 U/kg/day) and was followed up regularly. At the time of writing, the child had been treated for 6 months and was 7 years and 3 months old with a height of 106.3 cm (-3.69 SDS), which was a height increase of 6.3 cm. The patient did not complain of discomfort during treatment and presented normal laboratory tests results. Twenty-two children with FHS treated with rhGH were included in the literature review, and most of these patients demonstrated an increase in height SDS without adverse effects. Conclusion: Short stature, delayed skeletal maturation, impaired language expression, intellectual deficits, and peculiar facial features are the main clinical features of FHS. rhGH can be used as a treatment to increase height in patients with FHS, but its effectiveness and safety still need to be monitored in larger sample sizes over longer periods of time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bo, Jiang, Zheng and Sun.)

Floating-Harbor syndrome is a rare autosomal dominant genetic disorder associated with SRCAP mutation. To date, approximately 50 cases of Floating-Harbor syndrome have been reported, but none have been reported in Korea yet. Floating-Harbor syndrome is characterized by delayed bony maturation, unique facial features, and language impairment. Here, we present a 6-year-old boy with a triangular face, deep-set protruding eyes, low-set ears, wide nose with narrow nasal bridge, short philtrum, long thin lips, clinodactyly, and developmental delay that was transferred to our pediatric clinic for genetic evaluation. He showed progressive delay in the area of language and cognition-adaption as he grew. He had previously undergone chromosomal analysis at another hospital due to his language delay, but his karyotype was normal. We performed targeted exome sequencing, considering several syndromes with similar phenotypes. Library preparation was performed with the TruSight One sequencing panel, which enriches the sample for about 4,800 genes of clinical relevance. Massively parallel sequencing was conducted with NextSeq. An identified variant was confirmed by Sanger sequencing of the patient and his parents. Finally, the patient was confirmed as the first Korean case of Floating-Harbor syndrome with a novel SRCAP (Snf2 related CREBBP activator protein) mutation (c.7732dupT, p.Ser2578Phefs*6), resulting in early termination of the protein; it was not found in either of his healthy parents or a control population. To our knowledge, this is the first study to describe a boy with Floating-Harbor syndrome with a novel SRCAP mutation diagnosed by targeted exome sequencing in Korea.