PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：包含8基因的主要促进子超家族结构域（MFSD8）中的双等位基因变体与不同的临床表现相关，从典型的7型晚期婴儿神经元类脂褐菌病（CLN7疾病）到孤立的成人发作性视网膜营养不良。经典的晚期婴儿CLN7疾病是一种严重的，罕见的神经系统疾病，发病年龄通常在2到6岁之间，表现为癫痫发作和/或认知衰退。它的临床过程是渐进的，导致过早死亡,通常包括由于严重的视网膜营养不良导致的视力丧失。在极少数情况下,MFSD8的致病变异可能与发病年龄可变的孤立的非综合征性黄斑营养不良有关，其中疾病过程主要或完全影响黄斑的视锥，并且没有神经或神经精神表现。
方法：在这里，我们对4名成年发病患者进行了纵向研究，这些患者的4个MFSD8变异体均为双等位基因。
结果：两名无亲缘关系的患者在检查时出现成人共济失调和黄斑营养不良，在MFSD8NM_152778.4：c.935T>Cp。（Ile312Thr）中具有新的变体纯合子。另外两名患者在成年期出现视觉症状，其中之一在视觉症状出现数年后出现轻度至中度小脑共济失调。
结论：我们的观察扩大了对双等位基因致病性MFSD8变异的认识，并证实这些变异与一系列更异质性的临床表型相关。在MFSD8相关疾病中，成人发作的隐性共济失调可能是表现，也可能与视网膜营养不良合并发生。
方法：在这里，我们对4名成年发病患者进行了纵向研究，这些患者的4个MFSD8变异体均为双等位基因。
结果：两名无亲缘关系的患者在检查时出现成人共济失调和黄斑营养不良，在MFSD8NM_152778.4：c.935T>Cp。（Ile312Thr）中具有新的变体纯合子。另外两名患者在成年期出现视觉症状，其中之一在视觉症状出现数年后出现轻度至中度小脑共济失调。
结论：我们的观察扩大了对双等位基因致病性MFSD8变异的认识，并证实这些变异与一系列更异质性的临床表型相关。在MFSD8相关疾病中，成人发作的隐性共济失调可能是表现，也可能与视网膜营养不良合并发生。
