Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Two novel variants and five known variants were found in a total of ten unrelated Middle Eastern families.

Six months' follow-up of combined phacoemulsification-kahook dual blade excisional goniotomy.

PURPOSE: This study reports on the combination of excisional goniotomy and cataract extraction in the management of glaucoma in terms of intraocular pressure (IOP) and glaucoma medication reduction. METHODS: This is a retrospective case series. Twenty-eight eyes of 22 patients with the diagnosis of cataract and ocular hypertension or glaucoma of any stage underwent combined phacoemulsification and Kahook Dual Blade (KDB) goniotomy, between March 2019 and September 2020. The parameters evaluated were postoperative best-corrected visual acuity, mean IOP reduction, number of IOP-lowering medications, and the surgical success rate defined as IOP reduction >20% and/or reduction in glaucoma medications >1. RESULTS: The mean IOP reduction at 6 months was 4.5 mmHg (P = 0.0007), which translates to 24.9% reduction from preoperative IOP. The mean preoperative number of glaucoma medications was 2.9 ± 1.0 (median of 3). It was reduced to 1.1 ± 1.1 (median of 1.5), 1.46 ± 1.17 (median of 2), 1.44 ± 1.28 (median of 2), and 1.56 ± 1.28 (median of 2) at 1 week, 1 month, 3 months, and 6 months, respectively. Twenty-nine percent (8/28) of the patients were off glaucoma medications at 6 months and 46% (13/28) had a reduction of more than 50% of their glaucoma medications. CONCLUSION: Combined phacoemulsification-KDB excisional goniotomy may be an effective and safe alternative to more invasive filtering surgery in glaucoma patients of any stage.