Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants
Abstract 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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-02-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.2058 |
| _version_ | 1797903419554398208 |
|---|---|
| author | Melissa Daou Mirna Souaid Tony Yammine Issam Khneisser Hicham Mansour Nabiha Salem Antony Nemr Johnny Awwad Adib Moukarzel Chantal Farra |
| author_facet | Melissa Daou Mirna Souaid Tony Yammine Issam Khneisser Hicham Mansour Nabiha Salem Antony Nemr Johnny Awwad Adib Moukarzel Chantal Farra |
| author_sort | Melissa Daou |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T09:32:38Z |
| format | Article |
| id | doaj.art-f88d23c7c2c04489b339ace80cf136a8 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-10T09:32:38Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-f88d23c7c2c04489b339ace80cf136a82023-02-18T19:05:42ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-02-01112n/an/a10.1002/mgg3.2058Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variantsMelissa Daou0Mirna Souaid1Tony Yammine2Issam Khneisser3Hicham Mansour4Nabiha Salem5Antony Nemr6Johnny Awwad7Adib Moukarzel8Chantal Farra9Medical Genetics Unit Saint Joseph University Beirut LebanonMedical Genetics Unit Saint Joseph University Beirut LebanonMedical Genetics Unit Saint Joseph University Beirut LebanonMedical Genetics Unit Saint Joseph University Beirut LebanonDepartment of Pediatrics Saint Georges Hospital Beirut LebanonMedical Genetics Unit Saint Joseph University Beirut LebanonMedical Genetics Unit Saint Joseph University Beirut LebanonDepartement of Obstetrics and Gynecology American University of Beirut Medical Center Beirut LebanonDepartment of Pediatrics Hotel Dieu de France Beirut LebanonMedical Genetics Unit Saint Joseph University Beirut LebanonAbstract 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.https://doi.org/10.1002/mgg3.2058argininosuccinate synthetaseASS1citrullinemia type 1 |
| spellingShingle | Melissa Daou Mirna Souaid Tony Yammine Issam Khneisser Hicham Mansour Nabiha Salem Antony Nemr Johnny Awwad Adib Moukarzel Chantal Farra Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants Molecular Genetics & Genomic Medicine argininosuccinate synthetase ASS1 citrullinemia type 1 |
| title | Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants |
| title_full | Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants |
| title_fullStr | Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants |
| title_full_unstemmed | Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants |
| title_short | Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants |
| title_sort | analysis of ass1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants |
| topic | argininosuccinate synthetase ASS1 citrullinemia type 1 |
| url | https://doi.org/10.1002/mgg3.2058 |
| work_keys_str_mv | AT melissadaou analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT mirnasouaid analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT tonyyammine analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT issamkhneisser analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT hichammansour analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT nabihasalem analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT antonynemr analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT johnnyawwad analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT adibmoukarzel analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants AT chantalfarra analysisofass1geneintenunrelatedmiddleeasternfamilieswithcitrullinemiatype1identifiesrareandnovelvariants |