PDF(Pubmed)
Abstract：
Biallelic variants in SUMF1 are associated with multiple sulfatase deficiency (MSD), a rare lysosomal storage disorder typically diagnosed in early infancy or childhood, marked by severe neurodegeneration and early mortality. We present clinical and molecular characterisation of three unrelated patients aged 13 to 58 years with milder clinical manifestations due to SUMF1 disease variants, including two adult patients presenting with apparent non-syndromic retinal dystrophy. Whole genome sequencing identified biallelic SUMF1 variants in all three patients; Patient 1 homozygous for a complex allele c.[290G>T;293T>A]; p.[(Gly97Val);(Val98Glu)], Patient 2 homozygous for c.866A>G; p.(Tyr289Cys), and Patient 3 compound heterozygous for c.726-1G>C and p.(Tyr289Cys). Electroretinography indicated a rod-cone dystrophy with additional possible inner retinal dysfunction in all three patients. Biochemical studies confirmed reduced, but not absent, sulfatase enzyme activity in the absence of extra-ocular disease (Patient 1) or only mild systemic disease (Patients 2, 3). These cases are suggestive that non-null SUMF1 genotypes can cause an attenuated clinical phenotype, including retinal dystrophy without systemic complications, in adulthood.
摘要：
SUMF1的双等位基因变异体与多发性硫酸酯酶缺乏症（MSD）有关，一种罕见的溶酶体贮积症，通常在婴儿早期或儿童时期被诊断出来，以严重的神经变性和早期死亡为标志。我们介绍了三名年龄在13至58岁之间的无关患者的临床和分子特征，这些患者由于SUMF1疾病变异而具有较温和的临床表现。包括两名表现为明显的非综合征性视网膜营养不良的成年患者。全基因组测序鉴定了所有三名患者的双等位基因SUMF1变体；患者1为复杂等位基因c。[290G>T;293T>A]；p。[（Gly97Val）；（Val98Glu）]，患者2纯合子，c.86A>G；p.（Tyr289Cys），和患者3的化合物杂合子为c.726-1G>C和p.(Tyr289Cys)。视网膜电描记术表明，所有三名患者均存在视锥营养不良，并可能存在内部视网膜功能障碍。生化研究证实减少，但不是缺席，在没有眼外疾病（患者1）或仅轻度全身性疾病（患者2、3）的情况下，硫酸酯酶的活性。这些病例提示非无效SUMF1基因型可导致临床表型减弱，包括无全身并发症的视网膜营养不良,在成年。
