双偶联MFSD8变体患者的黄斑病变和成人型共济失调

IF 1.5 4区 医学 Q4 GENETICS & HEREDITY
Sigurd Dobloug, Ulrika Kjellström, Glenn Anderson, Emily Gardner, Sara E Mole, Jayesh Sheth, Andreas Puschmann
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引用次数: 0

摘要

背景:含主要促进因子超家族结构域 8 基因(MFSD8)的双叶变体与不同的临床表现有关,这些临床表现包括典型的晚发型婴幼儿神经细胞类脂质沉着病 7 型(CLN7 病)和孤立的成人发病型视网膜营养不良。典型的晚幼年CLN7病是一种严重、罕见的神经系统疾病,发病年龄通常在2至6岁之间,表现为癫痫发作和/或认知能力退化。该病的临床病程呈进行性发展,可导致过早死亡,并常常因严重的视网膜营养不良而导致视力丧失。在极少数病例中,MFSD8的致病变体可能与发病年龄不一的孤立性非综合征黄斑营养不良症有关,这种疾病主要或完全影响黄斑的视锥,而且没有神经或神经精神方面的表现:结果:两名无血缘关系的成年共济失调患者在检查时发现黄斑营养不良,他们都是MFSD8 NM_152778.4中一个新变异的同卵双生者:c.935T>C p.(Ile312Thr)。另外两名患者在成年后出现视觉症状,其中一人在出现视觉症状数年后出现轻度至中度小脑共济失调:我们的观察结果扩展了人们对双倍拷贝致病性 MFSD8 变体的认识,并证实这些变体与一系列异质性临床表型相关。在MFSD8相关疾病中,成人发病型隐性共济失调可能是主要表现,也可能与视网膜营养不良同时发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Maculopathy and adult-onset ataxia in patients with biallelic MFSD8 variants.

Background: Biallelic variants in the major facilitator superfamily domain containing 8 gene (MFSD8) are associated with distinct clinical presentations that range from typical late-infantile neuronal ceroid lipofuscinosis type 7 (CLN7 disease) to isolated adult-onset retinal dystrophy. Classic late-infantile CLN7 disease is a severe, rare neurological disorder with an age of onset typically between 2 and 6 years, presenting with seizures and/or cognitive regression. Its clinical course is progressive, leading to premature death, and often includes visual loss due to severe retinal dystrophy. In rare cases, pathogenic variants in MFSD8 can be associated with isolated non-syndromic macular dystrophy with variable age at onset, in which the disease process predominantly or exclusively affects the cones of the macula and where there are no neurological or neuropsychiatric manifestations.

Methods: Here we present longitudinal studies on four adult-onset patients who were biallelic for four MFSD8 variants.

Results: Two unrelated patients who presented with adult-onset ataxia and had macular dystrophy on examination were homozygous for a novel variant in MFSD8 NM_152778.4: c.935T>C p.(Ile312Thr). Two other patients presented in adulthood with visual symptoms, and one of these developed mild to moderate cerebellar ataxia years after the onset of visual symptoms.

Conclusions: Our observations expand the knowledge on biallelic pathogenic MFSD8 variants and confirm that these are associated with a spectrum of more heterogeneous clinical phenotypes. In MFSD8-related disease, adult-onset recessive ataxia can be the presenting manifestation or may occur in combination with retinal dystrophy.

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来源期刊
Molecular Genetics & Genomic Medicine
Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.20
自引率
0.00%
发文量
241
审稿时长
14 weeks
期刊介绍: Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.
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