目标：尼曼-皮克病A型（NPDA，MIM：257200）是由溶酶体酸性鞘磷脂酶（ASM）缺乏症引起的常染色体隐性遗传性鞘磷脂症。据报道，位于染色体11p15的一组基因是印迹基因，如TSSC5，TSSC3和ZNF215侧翼SMPD1基因。最近的一些研究报道，SMPD1基因是父系印迹的，并且是母系优先表达的。
方法：一个患有严重贫血的5个月大男孩，肝脾和骨髓泡沫细胞是从一对完整的表亲中招募的。为了确定男孩是否患有NPDA，对包括先证者在内的该谱系的可用个体进行ASM活性和SMPD1基因测序，他的父母和妹妹。先证者和父母的ASM活性显示缺乏（17.7nmol/h/g蛋白）和约50％降低（83.3nmol/h/g蛋白），分别,与正常对照组相比（204.5nmol/h/g蛋白）。先证者中的SMPD1基因测序显示纯合突变c.1420_1421del，这导致开放阅读移码和提前终止密码子。该家族的父母和一些个体在该基因座处表现出杂合突变。为了研究SMPD1基因是否像以前报道的那样被印记，在整个家族成员中研究了RNA水平的表达。具有c.1420_1421del杂合突变的成员表明，父系和母系遗传等位基因均表达。
结论：这项研究报道了SMPD1基因中的c.1420_1421del突变，该突变导致ASM活性降低，并且该基因座在杂合受试者中双等位基因表达，暗示SMPD1在该家族中没有印记。
OBJECTIVE: Niemann-Pick disease type A (NPDA, MIM: 257200) is an autosomal recessive sphingolipidosis caused by lysosomal acid sphingomyelinase (ASM) deficiency. A cluster of genes located at chromosome 11p15 have been reported to be imprinted genes, such as TSSC5, TSSC3, and ZNF215 that flanking SMPD1 gene. It was reported by a few recent studies that SMPD1 gene was paternally imprinted and maternally preferentially expressed.
METHODS: A five-month-old boy with severe anemia, hepatosplenomegly and bone marrow foam cells was recruited from a complete cousin couple. To determine whether boy suffered from NPDA, ASM activity and SMPD1 gene sequencing were performed on available individuals of this pedigree including the proband, his parents and sister. The ASM activities of proband and parents showed deficiency (17.7 nmol/h/g-protein) and about 50% decreased (83.3 nmol/h/g-protein), respectively, compared with normal controls (204.5 nmol/h/g-protein). SMPD1 gene sequencing in the proband revealed a homozygous mutation c.1420_1421del, which leads to an open reading frameshift and a premature stop codon. The parents and some individuals of this family demonstrated heterozygous mutation at this locus. To investigate whether SMPD1 gene is imprinted as reported previously, the expression of RNA level was studied in the whole family members available. The members with heterozygous mutation for c.1420_1421del showed that both paternal and maternal inherited alleles were expressed.
CONCLUSIONS: This study reported a c.1420_1421del mutation in SMPD1 gene which caused ASM activity decrease and this locus was biallelically expressed in heterozygous subjects implicating SMPD1 is not imprinted in this family.
