کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2813662 1569467 2016 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel SMARCAL1 missense mutation that affects splicing in a severely affected Schimke immunoosseous dysplasia patient
ترجمه فارسی عنوان
یک جهش جدید نادرست SMARCAL1 که بر اسپلایزینگ در یک بیمار مبتلا به دیسپلازی ایمونوسیز Schimke به شدت آسیب دیده تاثیر می گذارد
کلمات کلیدی
SMARCAL1؛ SIOD؛ دیسپلازی اسکلتی؛ نفروپاتی؛ نقص ایمنی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی ژنتیک
چکیده انگلیسی

Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive disease characterized by skeletal dysplasia, focal segmental glomerulosclerosis, renal failure and immunodeficiency. In this work, we report the molecular studies undertaken in a severely affected SIOD patient that died at six years old due to nephropathy. The patient was screened for mutations using a targeted skeletal dysplasias panel. A homozygous novel missense mutation was identified, c.1615C > G (p.[Leu539Val]) that was predicted as mildly pathogenic by in silico pathogenicity prediction tools. However, splicing prediction software suggested that this variant may create a new splicing donor site in exon 9, which was subsequently confirmed using a minigene assay in HEK293 cells. Thus, the splicing alteration, c.1615C > G; r.1615c > g, 1615_1644del; (p.[Leu539_Ile548del]), results in the loss of 10 amino acids of the HARP-ATPase catalytic domain and the RPA-binding domain. Several studies have demonstrated a weak genotype-phenotype correlation among such patients. Thus, the molecular characterization has helped us to understand why a predicted weakly pathogenic missense mutation results in severe SIOD and should be considered in similar scenarios.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medical Genetics - Volume 59, Issue 8, August 2016, Pages 363–366
نویسندگان
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