MINPP1-Related Pontocerebellar Hypoplasia in Five New Patients: Identification of Three Novel Variants and Further Phenotype Delineation.

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Sherif F Abdel Ghafar, Amr E Ahmed, Eman T Mohammed, Ghada M H Abdel-Salam, Maha S Zaki, Mohamed S Abdel-Hamid
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引用次数: 0

Abstract

MINPP1-related pontocerebellar hypoplasia (PCH) is a rare neurodevelopmental disorder characterized by microcephaly, profound developmental delay, and a distinct neuroimaging pattern. To date, only 21 patients from 13 unrelated families have been reported. Herein, we describe five patients from four Egyptian families with homozygous MINPP1 variants. All patients presented with global developmental delay, microcephaly, hypotonia, nystagmus, severe motor impairment, seizures, and intellectual disability. Interestingly, all patients exhibited dysmorphic facies, characterized by a high forehead, long philtrum, smooth philtrum, thin upper lip vermilion, broad chin, and low-set ears. Additional variable findings were optic atrophy, strabismus, feeding difficulties, and genital anomalies. Brain MRI showed cerebellar and pontine hypoplasia, thin corpus callosum, cortical atrophic changes, white matter signal, enlarged ventricles, and striking basal ganglia hypoplasia. Exome sequencing identified four MINPP1 variants, including three novel variants (p.Trp68Ter, p.Trp141Ter, and p.Val434_Gln435dup). All variants are localized within functionally critical domains of the protein and were either absent or extremely rare in public databases. Our study increases the number of affected individuals with MINPP1 variants and reinforces the clinical and brain imaging features of the disorder. In addition, the specific facial gestalt noted in our patients along with the basal ganglia changes appear characteristic and might point to the diagnosis of this type of PCH.

5例新患者中与minpp1相关的桥小脑发育不全:三个新变体的鉴定和进一步的表型描述。
minpp1相关桥小脑发育不全(PCH)是一种罕见的神经发育障碍,以小头畸形、严重发育迟缓和独特的神经影像学模式为特征。迄今为止,仅报告了来自13个无血缘关系家庭的21例患者。本文中,我们描述了来自4个埃及家庭的5例MINPP1纯合子变异患者。所有患者均表现为整体发育迟缓、小头畸形、张力低下、眼球震颤、严重运动障碍、癫痫发作和智力残疾。有趣的是,所有患者都表现出畸形相,其特征是额头高,中心长,中心光滑,上唇薄,朱红色,下巴宽,耳朵低。其他可变的发现是视神经萎缩、斜视、进食困难和生殖器异常。脑MRI表现为小脑和脑桥发育不全,胼胝体薄,皮质萎缩改变,白质信号,脑室增大,基底节区发育不全。外显子组测序鉴定出4个MINPP1变体,包括3个新变体(p.Trp68Ter、p.Trp141Ter和p.Val434_Gln435dup)。所有变异都定位在蛋白质的功能关键区域内,在公共数据库中要么不存在,要么极其罕见。我们的研究增加了MINPP1变异的受影响个体的数量,并加强了该疾病的临床和脑成像特征。此外,在我们的患者中,特定的面部格式塔以及基底神经节的变化似乎是特征性的,可能指向这种类型的PCH的诊断。
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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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