[Clinical characterization and mutation identification for multiple sulfatase deficiency patients in China].
OBJECTIVE
Multiple sulfatase deficiency is a rare autosomal recessively inherited lysosomal storage disorder characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The aim of this study was to explore the clinical manifestations, enzyme activities and SUMF1 gene mutations in two Chinese patients with multiple sulfatase deficiency.


METHODS
One boy and one girl from two families were studied. Both patients presented with mental retardation, mild coarse facial features, a neurodegenerative course of disease with loss of sensory and motor function after 2 years of age, ichthyosis and skeletal abnormalities (kyphosis or/and scoliosis). Clinical characteristics indicate multiple sulfatase deficiency.Sulfatases activities in blood leucocytes, plasma or cultured fibroblast of the patients were measured.Genomic DNAs were extracted from peripheral blood leukocytes from the patients and their parents. All SUMF1 gene exons and intron-exon boundaries were amplified by PCR and subjected for direct sequencing.


RESULTS
In case 1, five sulfatases activities of blood leucocytes and four sulfatases of cultured skin-fibroblasts were analyzed.In case 2, three sulfatases activities of blood leucocytes were tested.Significantly decreased sulfatases activities confirmed the diagnosis of multiple sulfatase deficiency.On SUMF1 gene, c.793_794 insATG (p. P265X)/ c.1045C>T (p.R349W) in case 1 and c.451A>G (p.K151E)/ c.1046G>C (p.R349Q) in case 2 were detected, respectively. Three novel mutations c.793_794insAGT, c.1046G>C and c.451A>G were identified.


CONCLUSIONS
Multiple sulfatase deficiency usually results in multi-organ damage, especially neurologic, skeletal and skin.Sulfatases assay and SUMF1 gene analysis are necessary for the diagnosis. Two Chinese cases with multiple sulfatase deficiency were firstly reported. Three novel mutations were found.It should be considered that the mutation profile of SUMF1 gene in Chinese patients is different from other populations.
Department of Medical Genetics,Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, WHO Collaborating Project for Community Control of Hereditary Disease, Beijing 100005, China.
Yan
Y
Meng
Wei-min
WM
Zhang
Hui-ping
HP
Shi
Feng-xia
FX
Yao
Zheng-qing
ZQ
Qiu
Tao
T
Yang
Shi-min
SM
Zhao
Email: hsz_pumc@ibms.pumc.edu.cn.
Shang-zhi
SZ
Huang
D000015:Abnormalities, Multiple; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D052517:Multiple Sulfatase Deficiency Disease / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D016133:Polymerase Chain Reaction; D013429:Sulfatases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D050862:Oxidoreductases Acting on Sulfur Group Donors; C480483:SUMF1 protein, human; D013429:Sulfatases