Hao-Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum,Clinical Genetics

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Hao-Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum
Clinical Genetics ( IF 2.9 ) Pub Date : 2024-01-14 , DOI: 10.1111/cge.14480
Moritz Claudius Wimmer ₁ , Heiko Brennenstuhl ₁ , Steffen Hirsch ₁ , Laura Dötsch ₁ , Samy Unser ₁ , Pilar Caro ₁ , Christian Patrick Schaaf _{1,

2}

Affiliation

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.

中文翻译：

豪泉综合征：32 名新患者揭示了对临床谱的新见解

hao-fountain 综合征 (HAFOUS, OMIM: #616863) 是一种神经发育障碍，由编码USP7的基因 USP7 的致病性变异引起，USP7 是一种参与多种关键细胞稳态机制和最近描述的 MUST 复合体的蛋白质。对 HAFOUS 的表型了解还不够，但非常需要更好地了解疾病谱、基因型-表型相关性和疾病轨迹。我们现在介绍了另外 32 名个体的更大队列，并提供了有关先前报告的 6 名个体的进一步临床信息。进行了一项基于问卷的研究，以更清楚地表征Hao-Fountain综合征的表型，突出新的特征，并更好地区分该疾病与相关的神经发育障碍。除了确认之前描述的特征之外，我们还报告了一部分个体的食欲亢进和体重增加。 HAFOUS 患者出生并发症、先天性异常和疼痛阈值异常的发生率增加。言语障碍是浩泉综合征的一个潜在标志。认知测试报告显示平均智力功能处于边缘状态，尽管有些人的得分处于智力障碍范围内。最后，我们创建了特定于综合症的严重程度评分。该评分既不表明临床严重程度存在性别或年龄特异性差异，但强调了当氨基酸变化与 USP7 蛋白的催化结构域共定位时更严重的结果。

更新日期：2024-01-14

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