背景:1型瓜氨酸血症(CTLN1)是一种由精氨酸琥珀酸合成酶(ASS)缺乏引起的罕见常染色体隐性遗传疾病。表现从急性新生儿或“经典”形式到较温和,迟发性,或“非常规”形式。迄今为止,据报道,位于染色体9q43.11(OMIM#215700)上的ASS1基因中超过93个变异体负责CTLN1.它们的发病率和分布因地理起源和种族而异,和相关性,虽然没有明确的描述,已在疾病的基因型和表型之间确立。不过,在中东,CTLN1的国家描述仍然缺乏。
方法:总共十个不相关的中东家庭,五个黎巴嫩人,两名叙利亚人,和三名伊拉克人患有瓜氨酸血症指数病例,包括在这项研究中。经知情同意,从索引患者及其父母和兄弟姐妹的全血中提取DNA。通过ASS1基因的Sanger测序进行遗传分析。
结果:确定了7种不同的变体。两个新颖的变体,c.286C>A(p。(Pro96Thr),未分析的RNA)外显子5和缺失c.685_6886del(p。(Lys229Glyfs*4),RNA未分析)在外显子10中,在一个黎巴嫩人和一个叙利亚家庭中发现,分别,并与早发和严重临床表现相关。其他五个已知的变体:c.535T>C(p。(Trp179Arg),未分析的RNA)外显子8,c.787G>A(p。(Val263Met),未分析的RNA)在外显子12中,c.847G>A(p。(Glu283Lys),未分析的RNA)外显子13,c.910C>T(p。(Arg304Trp),未分析的RNA)在外显子13中,并且c.1168G>A(p。(Gly390Arg),RNA未分析)外显子15,在黎巴嫩人中发现,叙利亚,和伊拉克家庭,并与不同的临床表现相关。
结论:在总共十个不相关的中东家族中发现了两个新变体和五个已知变体。
Citrullinemia type 1 (CTLN1) is a rare autosomal recessive disease caused by argininosuccinate synthetase (ASS) deficiency. Manifestations vary from the acute neonatal or \"classic\" form to a milder, late-onset, or \"unconventional\" form. To date, more than 93 variants in the ASS1 gene located on chromosome 9q43.11 (OMIM #215700) are reportedly responsible for CTLN1. Their incidence and distribution vary according to geographic origins and ethnicity, and a correlation, although not clearly delineated, has been established between the genotype and the phenotype of the disease. Though, in the Middle East, national descriptions of CTLN1 are still lacking.
A total of ten unrelated Middle Eastern families, five Lebanese, two Syrians, and three Iraqis with citrullinemia index cases, were included in this study. Upon informed consent, DNA was extracted from the whole blood of the index patients as well as their parents and siblings. Genetic analysis was carried out by Sanger sequencing of the ASS1 gene.
Seven different variants were identified. Two novel variants, c.286C>A (p.(Pro96Thr), RNA not analyzed) in exon 5 and deletion c.685_688+6del(p.(Lys229Glyfs*4), RNA not analyzed) in exon 10, were found in one Lebanese and one Syrian family, respectively, and were correlated with early-onset and severe clinical presentation. Five other known variants: c.535T>C (p.(Trp179Arg), RNA not analyzed) in exon 8, c.787G>A (p.(Val263Met), RNA not analyzed) in exon 12, c.847G>A (p.(Glu283Lys), RNA not analyzed) in exon 13, c.910C>T (p.(Arg304Trp), RNA not analyzed) in exon 13, and c.1168G>A (p.(Gly390Arg), RNA not analyzed) in exon 15, were found in Lebanese, Syrian, and Iraqi families, and were associated with diverse clinical presentations.
Two novel variants and five known variants were found in a total of ten unrelated Middle Eastern families.