Bashyam M D, Chaudhary A K, Kiran M, Reddy V, Nagarajaram H A, Dalal A, Bashyam L, Suri D, Gupta A, Gupta N, Kabra M, Puri R D, RamaDevi R, Kapoor S, Danda S
Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Clin Genet. 2014 Dec;86(6):530-8. doi: 10.1111/cge.12316. Epub 2013 Dec 20.
Farber lipogranulomatosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the ASAH1 gene. In the largest ever study, we identified and characterized ASAH1 mutations from 11 independent Farber disease (FD) families. A total of 13 different mutations were identified including 1 splice, 1 polypyrimidine tract (PPT) deletion and 11 missense mutations. Eleven mutations were exclusive to the Indian population. The IVS6+4A>G splice and IVS5-16delTTTTC PPT deletion mutations resulted in skipping of exon 6 precluding thereby the region responsible for cleavage of enzyme precursor. A missense mutation (p.V198A) resulted in skipping of exon 8 due to inactivation of an exonic splicing enhancer (ESE) element. This is the first report of mutations affecting PPT and ESE in the ASAH1 gene resulting in FD.
法伯脂肪肉芽肿病是一种罕见的常染色体隐性溶酶体贮积症，由ASAH1基因突变引起。在有史以来规模最大的研究中，我们从11个独立的法伯病（FD）家庭中鉴定并表征了ASAH1基因突变。共鉴定出13种不同的突变，包括1种剪接突变、1种多嘧啶序列（PPT）缺失突变和11种错义突变。其中11种突变是印度人群所特有的。IVS6+4A>G剪接突变和IVS5-16delTTTTC PPT缺失突变导致外显子6跳跃，从而排除了负责酶前体切割的区域。一种错义突变（p.V198A）由于外显子剪接增强子（ESE）元件失活导致外显子8跳跃。这是关于ASAH1基因中影响PPT和ESE并导致FD的突变的首次报道。
