Correspondence on “Pathogenic variants in USP7 cause a neurodevelopmental disorder with speech delays, altered behavior, and neurologic anomalies” by Fountain et al.

Capra, Anna Paola; Agolini, Emanuele; Rosa, Maria Angela La; Novelli, Antonio; Briuglia, Silvana

doi:10.1038/s41436-020-00978-x

Cited by 7 publications

(11 citation statements)

References 5 publications

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“…In Zheng et al's paper, patent foramen ovale was also found in a patient; 15 similar congenital cardiac structural abnormalities have also been reported in individual patients, including mitral valve prolapse, patent ductus arteriosus, atrial septal defect, and ventriculomegaly. Besides, P1 had hearing loss in the right ear, which was the same as the previous report 12 13 ( Table 1 ).…”

Section: Discussionsupporting

confidence: 88%

“…By reviewing previous reports and comparing them with our patients, 11 12 13 14 15 we summarized the main clinical features and signs of Hao-Fountain syndrome in Table, including developmental delay/intellectual disability (30/31, 96.8%), speech delay (30/30, 100%), dysmorphic face (20/22, 84.6%), brain MRI anomalies (18/23, 78.3%), hypotonia (19/27, 70.8%), behavioral anomalies (19/27, 70.4%), eye abnormalities such as esotropia, myopia, strabismus, nystagmus (16/27, 59.3%), autism spectrum disorder (11/20, 55.0%), gastroesophageal reflux with feeding difficulties (11/20, 55.0% and 13/25, 52.0%, respectively). Abnormal behavior consisted of aggressive behavior, temper tantrums, impulsivity, compulsivity, stubbornness, manipulative behavior.…”

Section: Resultsmentioning

confidence: 98%

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Identification of Two Variants c.2697A > C and c.3305A > C in USP7 by Analysis of Whole-Exome Sequencing in Chinese Patients with Hao-Fountain Syndrome

Sun,

Li,

Zhang

et al. 2024

Glob Med Genet

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Background Variants of ubiquitin-specific protease 7 (USP7) gene in humans are associated with a neurodevelopmental disorder—Hao-Fountain syndrome, its core symptoms including developmental delay, intellectual disability, and speech delay. Other variable symptoms can affect multiple systems. In present study, we report two patients with core features from two unrelated consanguineous families originating from the Tianjin Children's Hospital. Methods and Results Genomic DNA was extracted from the peripheral blood samples collected from the probands with their family members and whole-exome sequencing (WES) was used to detect the pathogenic genes in the probands. Suspected variants were subsequently validated by Sanger sequencing. In family 1, WES revealed that the proband carried the de novo variant c.2697A > C (p.Leu899Phe) in USP7 (NM_003470.3). In family 2, WES identified the variant c.3305A > C (p.Asn1102Thr) in USP7 (NM_003470.3) from the proband. Conclusion We reported two cases of Hao-Fountain syndrome caused by novel USP7 variants. In addition, we report the first case of mosaicism with a USP7 variant in Chinese family. Our findings demonstrate the importance of WES in diagnosis of genetic diseases and expands the USP7 variants spectrum in Hao-Fountain syndrome. Moreover, we summarize the cases caused by USP7 variants in the literature. Our study can provide a vital reference for the diagnosis of future cases.

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 98%

Identification of Two Variants c.2697A > C and c.3305A > C in USP7 by Analysis of Whole-Exome Sequencing in Chinese Patients with Hao-Fountain Syndrome

Sun,

Li,

Zhang

et al. 2024

Glob Med Genet

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“…Hao-Fountain syndrome comes with different clinical aspects but less is known about the genital and fertility “area”; literature data show the possibility of endocrine complications (pubertal delay, autoimmune diseases), immunological deficit and predisposition to autoimmune diseases and a wide variety of cancers. Moreover, in this case, as suggested by Capra et al [ 24 ], the correct diagnosis allowed us to plan neuropsychiatric, endocrinological, immunological, cardiological, and potential oncological risk follow-up.…”

Section: Discussionmentioning

confidence: 58%

Hao-Fountain syndrome and genital disorders: report of a new possible association

et al. 2022

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Background Hao-Fountain syndrome is a neurodevelopmental disorder characterized by global developmental delay, variably impaired intellectual development with significant speech delay and, in some males patients, it has been reported an association with hypogonadism. At present less than 50 cases are reported in literature. Case presentation We report a case of this rare syndrome in a young female with isolated tubal torsion; our patients had different hospitalizations without treatment but during the last episode we decide to perform an abdominal surgical explortion. This is the first case in Literature with a new USP7 mutation. Conclusions This case opens new perspective in this rare syndrome and a review approach to isolated tubal torsion. These symptoms should be always well checked.

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“…If not stated otherwise, the frequency of the symptoms always describes the prevalence in all publicly accessible cases, including patients described by Hao et 3,6,10,12,13 A severity score was developed based on the most frequently occurring clinical features. Where available, the score considers the range of severity, for example, one or two points based on the severity of the developmental delay.…”

Section: Methodsmentioning

confidence: 99%

“…6 In subsequent case reports, six more patients were added to the publicly available cohort. [10][11][12][13] These new cases implicate a higher variability of the clinical spectrum, as fetal complications, 10,11 congenital heart defects, 10 and isolated tubal torsion 12 were first described. Next to these specific items, the clinical presentation of these patients is mainly according to the phenotype described previously.…”

mentioning

confidence: 99%

Hao‐Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum

Wimmer,

Brennenstuhl,

Hirsch

et al. 2024

Clinical Genetics

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Hao‐Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the gene USP7 coding for USP7, a protein involved in several crucial cellular homeostatic mechanisms and the recently described MUST complex. The phenotype of HAFOUS is insufficiently understood, yet there is a great need to better understand the spectrum of disease, genotype–phenotype correlations, and disease trajectories. We now present a larger cohort of 32 additional individuals and provide further clinical information about six previously reported individuals. A questionnaire‐based study was performed to characterize the phenotype of Hao‐Fountain syndrome more clearly, to highlight new traits, and to better distinguish the disease from related neurodevelopmental disorders. In addition to confirming previously described features, we report hyperphagia and increased body weight in a subset of individuals. HAFOUS patients present an increased rate of birth complications, congenital anomalies, and abnormal pain thresholds. Speech impairment emerges as a potential hallmark of Hao‐Fountain syndrome. Cognitive testing reports reveal borderline intellectual functioning on average, although some individuals score in the range of intellectual disability. Finally, we created a syndrome‐specific severity score. This score neither indicates a sex‐ nor age‐specific difference of clinical severity, yet highlights a more severe outcome when amino acid changes colocalize to the catalytic domain of the USP7 protein.

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Correspondence on “Pathogenic variants in USP7 cause a neurodevelopmental disorder with speech delays, altered behavior, and neurologic anomalies” by Fountain et al.

Cited by 7 publications

References 5 publications

Identification of Two Variants c.2697A > C and c.3305A > C in USP7 by Analysis of Whole-Exome Sequencing in Chinese Patients with Hao-Fountain Syndrome

Identification of Two Variants c.2697A > C and c.3305A > C in USP7 by Analysis of Whole-Exome Sequencing in Chinese Patients with Hao-Fountain Syndrome

Hao-Fountain syndrome and genital disorders: report of a new possible association

Hao‐Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum

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