Mirna Souaid - Academia.edu (original) (raw)
Papers by Mirna Souaid
Human Genetics, Dec 1, 2007
Journal of Cystic Fibrosis, Sep 1, 2008
Background: Cystic fibrosis is the most common autosomal recessive disorder in Caucasians. Little... more Background: Cystic fibrosis is the most common autosomal recessive disorder in Caucasians. Little has been reported on its occurrence in Arab and Lebanese populations where mutation distribution seems to differ from that of Europeans. We report on the occurrence of a frameshift mutation 4016insG in two Lebanese Muslim siblings, products of consanguineous parents. This mutation generates a stop codon instead of Arginine-1301 and has never been reported before. Methods: Both probands manifested early onset of severe respiratory and pancreatic involvement. DNA analysis was performed by PCR and sequencing for exons 1, 4, 10, 11, 20, 21 of the CFTR gene. Results: Both probands were found to be homozygous for the 4016insG. Their parents were both heterozygous for the same mutation. Conclusion: The frameshift mutation reported in this article is being described for the first time.
Molecular Genetics & Genomic Medicine, Jan 20, 2023
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Clinical Dysmorphology, Aug 20, 2020
Pediatrics Department, Hotel-Dieu de France University Hospital, Medical Genetics Unit and Medica... more Pediatrics Department, Hotel-Dieu de France University Hospital, Medical Genetics Unit and Medical Genetics Department, Hotel-Dieu de France University Hospital, Saint Joseph University, Beirut, Lebanon Correspondance to Chantal Farra, MD, American University of Beirut Medical center, Mar Mikhael, Beirut 11042020, Lebanon Tel: +961 03229913; fax: +961 1421 632 B.P.17-5208; e-mail: chantal.farra@usj.edu.lb
Hemoglobin, May 5, 2021
β-Thalassemia (β-thal) is highly prevalent among the Mediterranean populations. In Lebanon, the c... more β-Thalassemia (β-thal) is highly prevalent among the Mediterranean populations. In Lebanon, the carrier rate of the disease is estimated to be around 2.0-3.0%. In this retrospective study, we determined the spectrum of β-thal mutations in a total of 170 individuals from a sample of 140 Lebanese, Iraqi and Syrian refugee families in Lebanon, over a period from 2012 to 2018. Twenty-eight different β-globin gene mutations were identified. The most prevalent mutations were IVS-I-110 (G>A) (HBB: c.93-21G>A), IVS-II-1 (G>A) (HBB: c.315+1G>A), IVS-I-6 (T>C) (HBB: c.92+6T>C) and IVS-I-1 (G>A) (HBB: c.92+1G>A), accounting for the majority of mutations found in HBB mutations analysed in 250 alleles. Ten different β-globin gene mutations that were not previously described in Lebanon were identified in our study. These mutations include the IVS-II-848 (C>A) (HBB: c.316-3C>A), codons 9/10 (+T) (HBB: c.30_31insT), codon 15 (-T) (HBB: c.46delT), -86 (C>G) (HBB: c.-136C>G), Cap +22 (G>A) (HBB: c.-29G>A), -28 (A>C) (HBB: c.-78A>C), codon 7 (GAG>TAG) (HBB: c.22G>T), codon 26 (GAG>TAG) (HBB: c.79G>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codons 82/83 (-G) (HBB: c.250delG). Of these, six mutations [codons 9/10, codon 15 (-T), -86, codon 7, codon 26, codons 82/83) were identified in Lebanese samples only; one mutation (IVS-II-848) was identified in both Lebanese and Iraqis; and three mutations (Cap +22, -28, codons 41/42) were identified in Iraqi samples only. Further studies will help better delineate the spectrum of β-thal mutations among different ethnic groups, and provide crucial prevention strategies.
Ophthalmic Genetics, Jul 20, 2021
ABSTRACT Introduction Cataract is a major condition characterized by ocular lens opacification, r... more ABSTRACT Introduction Cataract is a major condition characterized by ocular lens opacification, resulting from alteration in the lens architecture, lens proteins or both. It is responsible for about one-third of infants’ blindness worldwide. Variants in the FYCO1 gene have been associated with autosomal recessive infantile cataract. Material and Methods We conducted whole exome sequencing (WES) in a nine months old male patient who was referred for genetic investigation because of infantile cataract. WES analysis revealed the presence of a homozygous pathogenic variant (c.2365C>T) in exon 8 of the FYCO1 gene. Results and Discussion This is the first report on a Lebanese infant with infantile cataract and cortical atrophy which was not previously reported, resulting from a novel homozygous FYCO1 variant; thus expanding the clinical phenotypic spectrum of FYCO1 involvement.
Research Square (Research Square), Mar 1, 2023
Background Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characte... more Background Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characterized by lack of pain perception with a wide spectrum of clinical signs such as anosmia and hyposmia. SCN9A gene variants were found to be associated with CIP. We here report on a family with three CIP affected patients referred for genetic investigations. Methods and Results Whole exome sequencing analysis revealed the presence of a novel nonsense, homozygous SCN9A pathogenic variant: SCN9A (NM_001365536.1): c.4633G > T, p.(Glu1545*) in exon 26. Conclusion Our three Lebanese patients had CIP, urinary incontinence and normal olfactory function while two of them also presented with osteoporosis and osteoarthritis; this association of features has not been previously reported in the literature. We hope that this report would contribute to a better delineation of the spectrum caused by SCN9A pathogenic variants.
Prenatal Diagnosis, Sep 1, 2008
The aim of the study was to assess the rate of acceptance of preimplantation genetic diagnosis (P... more The aim of the study was to assess the rate of acceptance of preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis in Lebanese women with previously affected children with homozygous beta-thalassemia. Women with a previously affected child attending a non governmentally funded thalassemia care center between 1 June 2005 and 31 May 2007 were offered a genetic counseling session. This was followed by administering a questionnaire through direct interview. All 97 women approached accepted to participate in the study (100% response rate). Sixty eight per cent of women considered PGD a better alternative to prenatal diagnosis. The most important perceived advantage of PGD was the avoidance of termination of an affected pregnancy. PGD is an acceptable alternative to conventional prenatal diagnosis in women at risk of conceiving a child affected with beta-thalassemia. This is particularly true in countries of the Middle-East where therapeutic abortions for fetal indications are prohibited by the law and religion.
Clinical Dysmorphology, Feb 2, 2023
Journal of Molecular and Genetic Medicine, 2018
Background: Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disorder characteriz... more Background: Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disorder characterized by a relentless clinical course with diagnosis usually established around three to four years of age. DMD is caused by mutations in the dystrophin gene, where deletions and duplications of one or more exons represent the bulk of related genetic aberrations. Aims and methods: Our aim in the current study is to analyze the frequency and the distribution pattern of deletions/duplications associated with dystrophin gene exons and assess the mean diagnostic age of DMD in a small Lebanese group of dystrophic patients suspected with DMD/BMD based on observed clinical features. Results and discussion: Among 52 samples analyzed, we identified 33 cases (63%) with deletions and two cases (4%) with duplications. Deletions were of variable sizes, ranging from 1 to 47 exons and occurred mostly (78%) in two deletion hotspots (HS), HS1 (18%) and HS2 (60%), covering exons 6-19 and 45-52 respectively. Single exon deletions were even further restricted (90%) to the deletion hotspots, mainly to HS2 (80%). The average age of DMD molecular diagnosis in our subject study was 7 years of age. Conclusion: Molecular analyses were consistent with those obtained in previous studies, with however an average age of DMD diagnosis significantly later than what is usually reported. Our study illustrates the need to implement early molecular diagnosis in order to institute optimal care, including available targeted treatments, for our patients.
Journal of pediatric genetics, Jul 20, 2020
17p13.3 microduplication syndrome has been associated with a clinical spectrum of phenotypes, and... more 17p13.3 microduplication syndrome has been associated with a clinical spectrum of phenotypes, and depending on the genes involved in the microduplication, it is categorized into two classes (Class I and Class II). We herein, describe two patients diagnosed with Class I 17p13.3 microduplication by BACs-on-Beads (BoBs) assay and further confirmed by fluorescence in situ hybridization (FISH). Our patients (Patient 1: 4-year-old male; Patient 2: 2-year-old male) presented with developmental delay, intellectual disability, and dysmorphic facial features. When compared with the literature, our patients manifested distinctive features (Patient 1: primary hypothyroidism; Patient 2: bilateral cryptorchidism) that were not previously described in the duplication 17p13.3 spectrum.
PubMed, Dec 24, 2009
In this article, we analyze the clinical and biological data concerning the autoimmune thyroid di... more In this article, we analyze the clinical and biological data concerning the autoimmune thyroid diseases in patients recruited in an endocrinology clinic at the university hospital center of Hôtel-Dieu de France between March 2005 and November 2005. We studied 121 patients (51 with Basedow disease and 70 with Hashimoto thyroiditis), between 13 and 68 years old, with a BMI of 24.68 kg/m2 and with a female predominance (105 women). Symptoms of hyperthyroidism represented the most frequent cause of consultation. The distribution of patients regarding their thyroid disease showed that 42.1% of patients had hyperthyroidism (only one patient had subclinical hyperthyroidism), 21.5% had a subclinical hypothyroidism, 28.1% had clinical hypothyroidism and 8.3% had euthyroid goiter. Half of the patients had at least a member of their family whith a thyroid disease. The autoimmune thyroid diseases are strongly associated to other autoimmune diseases and to repetitive spontaneous abortion. Thus, 39% of the married women had had at least one spontaneous abortion and 26.4% of the patients had one or more autoimmune disease associated to their thyroid disease; diabetes mellitus type 1 representing the most frequent one. Concerning the treatment, we remarked a remission of 30 patients (66.7%) with Basedow disease after 18 months of antithyroid drug treatment of 45 patients. In Hashimoto thyroiditis, we remarked a frequent evolution of patients with subclinical hypothyroidism to overt hypothyroidism when medical treatment was not initiated.
Annals of clinical and translational neurology, Jul 25, 2022
Journal of Community Genetics, Mar 6, 2012
This study aims to investigate the association of human leukocyte antigen (HLA) class II genes an... more This study aims to investigate the association of human leukocyte antigen (HLA) class II genes and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with autoimmune thyroid diseases in the Lebanese population. A total of 128 patients with autoimmune thyroid disease (55 with Graves' disease (GD) and 73 with Hashimoto's thyroiditis (HT)) were typed for HLA DQA1 (0301 and 0501) and DQB1 (0201, 0302, and 0303) and for 49A/G CTLA-4 using PCR-based sequence-specific priming methods. A total of 186 matched controls were typed for the same alleles and compared to the diseased population. Results showed no significant differences in HLA DQB1*0201 or DQB1*0301 allelic frequencies or CTLA-4 polymorphisms between patients and controls. For GD, there was a weak association with HLA DQB1*0302 [34.6% (19 of 55) vs. 21.5% (40 of 186), P00.048, odds ratio (OR)01.926, confidence interval (CI)00.999-3.715] and HLA DQB1*0302-DQA1*0501 haplotype [56.36% (31 of 55) vs. 40.8% (76 of 186), P00.042, OR01.870, CI01.018-3.433]. For HT, the frequencies of DQB1*0302-DQA1*0501 haplotype [28.8% (21of 73) vs. 14.5% (27 of 186), P00.008, OR02.378, CI01.241-4.558] and DQB1*0302-DQA1*0301 haplotype [60.2% (44 of 73) vs. 38.7% (72 of 186), P00.002, OR02.402, CI01.381-4.180] were significantly higher in patients. On the other hand, weak association was found between HT and DQA1*0301 allele [32.9% (24 of 73) vs. 20.9% (39 of 186), P00.044, OR01.846, CI01.011-3.373]. Findings show that DQB1*0302-DQA1*0501 and DQB1*0302-DQA1*0301 haplotypes may play a role in the pathogenesis of HT in the Lebanese population. For the 49A/G CTLA-4 polymorphism, no significant difference was found between patients and controls.
Annals of Human Genetics, Dec 9, 2021
Cystic fibrosis is the most common life-limiting autosomal recessive disease in western countries... more Cystic fibrosis is the most common life-limiting autosomal recessive disease in western countries with an incidence of 1:2500 in United States and 1:1000 in some European countries. Similar incidences were noted for the Middle East with variations from 1 in 2560 to 1 in 15,876 according to the degree of consanguinity. This is a preliminary systematic study that aims to assess the incidence and carrier rate of cystic fibrosis in the Middle Eastern Lebanese population; known for a high frequency of consanguinity. One hundred thirteen DNA samples were collected from neonatal blood cards obtained from newborns to healthy unrelated families with no previous history of Cystic fibrosis. Screening for Cystic Fibrosis-causing pathogenic variants was performed using next generation sequencing, and 17 different single nucleotide variants were detected, including six pathogenic and likely pathogenic. 5.5%-7% newborns were found to be carriers of a variant strongly suggestive of pathogenicity and comparable to published literature worldwide. This pilot analysis highlights the challenging interpretation of CFTR variants in a country underrepresented by large ethnic population analyses, and stresses the importance of premarital screening programs for Cystic fibrosis.
Molecular Biology Reports
Background Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characte... more Background Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characterized by lack of pain perception with a wide spectrum of clinical signs such as anosmia and hyposmia. SCN9A gene variants were found to be associated with CIP. We here report on a family with three CIP affected patients referred for genetic investigations. Methods and Results Whole exome sequencing analysis revealed the presence of a novel nonsense, homozygous SCN9A pathogenic variant: SCN9A (NM_001365536.1): c.4633G > T, p.(Glu1545*) in exon 26. Conclusion Our three Lebanese patients had CIP, urinary incontinence and normal olfactory function while two of them also presented with osteoporosis and osteoarthritis; this association of features has not been previously reported in the literature. We hope that this report would contribute to a better delineation of the spectrum caused by SCN9A pathogenic variants.
Human Genetics, Dec 1, 2007
Journal of Cystic Fibrosis, Sep 1, 2008
Background: Cystic fibrosis is the most common autosomal recessive disorder in Caucasians. Little... more Background: Cystic fibrosis is the most common autosomal recessive disorder in Caucasians. Little has been reported on its occurrence in Arab and Lebanese populations where mutation distribution seems to differ from that of Europeans. We report on the occurrence of a frameshift mutation 4016insG in two Lebanese Muslim siblings, products of consanguineous parents. This mutation generates a stop codon instead of Arginine-1301 and has never been reported before. Methods: Both probands manifested early onset of severe respiratory and pancreatic involvement. DNA analysis was performed by PCR and sequencing for exons 1, 4, 10, 11, 20, 21 of the CFTR gene. Results: Both probands were found to be homozygous for the 4016insG. Their parents were both heterozygous for the same mutation. Conclusion: The frameshift mutation reported in this article is being described for the first time.
Molecular Genetics & Genomic Medicine, Jan 20, 2023
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Clinical Dysmorphology, Aug 20, 2020
Pediatrics Department, Hotel-Dieu de France University Hospital, Medical Genetics Unit and Medica... more Pediatrics Department, Hotel-Dieu de France University Hospital, Medical Genetics Unit and Medical Genetics Department, Hotel-Dieu de France University Hospital, Saint Joseph University, Beirut, Lebanon Correspondance to Chantal Farra, MD, American University of Beirut Medical center, Mar Mikhael, Beirut 11042020, Lebanon Tel: +961 03229913; fax: +961 1421 632 B.P.17-5208; e-mail: chantal.farra@usj.edu.lb
Hemoglobin, May 5, 2021
β-Thalassemia (β-thal) is highly prevalent among the Mediterranean populations. In Lebanon, the c... more β-Thalassemia (β-thal) is highly prevalent among the Mediterranean populations. In Lebanon, the carrier rate of the disease is estimated to be around 2.0-3.0%. In this retrospective study, we determined the spectrum of β-thal mutations in a total of 170 individuals from a sample of 140 Lebanese, Iraqi and Syrian refugee families in Lebanon, over a period from 2012 to 2018. Twenty-eight different β-globin gene mutations were identified. The most prevalent mutations were IVS-I-110 (G>A) (HBB: c.93-21G>A), IVS-II-1 (G>A) (HBB: c.315+1G>A), IVS-I-6 (T>C) (HBB: c.92+6T>C) and IVS-I-1 (G>A) (HBB: c.92+1G>A), accounting for the majority of mutations found in HBB mutations analysed in 250 alleles. Ten different β-globin gene mutations that were not previously described in Lebanon were identified in our study. These mutations include the IVS-II-848 (C>A) (HBB: c.316-3C>A), codons 9/10 (+T) (HBB: c.30_31insT), codon 15 (-T) (HBB: c.46delT), -86 (C>G) (HBB: c.-136C>G), Cap +22 (G>A) (HBB: c.-29G>A), -28 (A>C) (HBB: c.-78A>C), codon 7 (GAG>TAG) (HBB: c.22G>T), codon 26 (GAG>TAG) (HBB: c.79G>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codons 82/83 (-G) (HBB: c.250delG). Of these, six mutations [codons 9/10, codon 15 (-T), -86, codon 7, codon 26, codons 82/83) were identified in Lebanese samples only; one mutation (IVS-II-848) was identified in both Lebanese and Iraqis; and three mutations (Cap +22, -28, codons 41/42) were identified in Iraqi samples only. Further studies will help better delineate the spectrum of β-thal mutations among different ethnic groups, and provide crucial prevention strategies.
Ophthalmic Genetics, Jul 20, 2021
ABSTRACT Introduction Cataract is a major condition characterized by ocular lens opacification, r... more ABSTRACT Introduction Cataract is a major condition characterized by ocular lens opacification, resulting from alteration in the lens architecture, lens proteins or both. It is responsible for about one-third of infants’ blindness worldwide. Variants in the FYCO1 gene have been associated with autosomal recessive infantile cataract. Material and Methods We conducted whole exome sequencing (WES) in a nine months old male patient who was referred for genetic investigation because of infantile cataract. WES analysis revealed the presence of a homozygous pathogenic variant (c.2365C>T) in exon 8 of the FYCO1 gene. Results and Discussion This is the first report on a Lebanese infant with infantile cataract and cortical atrophy which was not previously reported, resulting from a novel homozygous FYCO1 variant; thus expanding the clinical phenotypic spectrum of FYCO1 involvement.
Research Square (Research Square), Mar 1, 2023
Background Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characte... more Background Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characterized by lack of pain perception with a wide spectrum of clinical signs such as anosmia and hyposmia. SCN9A gene variants were found to be associated with CIP. We here report on a family with three CIP affected patients referred for genetic investigations. Methods and Results Whole exome sequencing analysis revealed the presence of a novel nonsense, homozygous SCN9A pathogenic variant: SCN9A (NM_001365536.1): c.4633G > T, p.(Glu1545*) in exon 26. Conclusion Our three Lebanese patients had CIP, urinary incontinence and normal olfactory function while two of them also presented with osteoporosis and osteoarthritis; this association of features has not been previously reported in the literature. We hope that this report would contribute to a better delineation of the spectrum caused by SCN9A pathogenic variants.
Prenatal Diagnosis, Sep 1, 2008
The aim of the study was to assess the rate of acceptance of preimplantation genetic diagnosis (P... more The aim of the study was to assess the rate of acceptance of preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis in Lebanese women with previously affected children with homozygous beta-thalassemia. Women with a previously affected child attending a non governmentally funded thalassemia care center between 1 June 2005 and 31 May 2007 were offered a genetic counseling session. This was followed by administering a questionnaire through direct interview. All 97 women approached accepted to participate in the study (100% response rate). Sixty eight per cent of women considered PGD a better alternative to prenatal diagnosis. The most important perceived advantage of PGD was the avoidance of termination of an affected pregnancy. PGD is an acceptable alternative to conventional prenatal diagnosis in women at risk of conceiving a child affected with beta-thalassemia. This is particularly true in countries of the Middle-East where therapeutic abortions for fetal indications are prohibited by the law and religion.
Clinical Dysmorphology, Feb 2, 2023
Journal of Molecular and Genetic Medicine, 2018
Background: Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disorder characteriz... more Background: Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disorder characterized by a relentless clinical course with diagnosis usually established around three to four years of age. DMD is caused by mutations in the dystrophin gene, where deletions and duplications of one or more exons represent the bulk of related genetic aberrations. Aims and methods: Our aim in the current study is to analyze the frequency and the distribution pattern of deletions/duplications associated with dystrophin gene exons and assess the mean diagnostic age of DMD in a small Lebanese group of dystrophic patients suspected with DMD/BMD based on observed clinical features. Results and discussion: Among 52 samples analyzed, we identified 33 cases (63%) with deletions and two cases (4%) with duplications. Deletions were of variable sizes, ranging from 1 to 47 exons and occurred mostly (78%) in two deletion hotspots (HS), HS1 (18%) and HS2 (60%), covering exons 6-19 and 45-52 respectively. Single exon deletions were even further restricted (90%) to the deletion hotspots, mainly to HS2 (80%). The average age of DMD molecular diagnosis in our subject study was 7 years of age. Conclusion: Molecular analyses were consistent with those obtained in previous studies, with however an average age of DMD diagnosis significantly later than what is usually reported. Our study illustrates the need to implement early molecular diagnosis in order to institute optimal care, including available targeted treatments, for our patients.
Journal of pediatric genetics, Jul 20, 2020
17p13.3 microduplication syndrome has been associated with a clinical spectrum of phenotypes, and... more 17p13.3 microduplication syndrome has been associated with a clinical spectrum of phenotypes, and depending on the genes involved in the microduplication, it is categorized into two classes (Class I and Class II). We herein, describe two patients diagnosed with Class I 17p13.3 microduplication by BACs-on-Beads (BoBs) assay and further confirmed by fluorescence in situ hybridization (FISH). Our patients (Patient 1: 4-year-old male; Patient 2: 2-year-old male) presented with developmental delay, intellectual disability, and dysmorphic facial features. When compared with the literature, our patients manifested distinctive features (Patient 1: primary hypothyroidism; Patient 2: bilateral cryptorchidism) that were not previously described in the duplication 17p13.3 spectrum.
PubMed, Dec 24, 2009
In this article, we analyze the clinical and biological data concerning the autoimmune thyroid di... more In this article, we analyze the clinical and biological data concerning the autoimmune thyroid diseases in patients recruited in an endocrinology clinic at the university hospital center of Hôtel-Dieu de France between March 2005 and November 2005. We studied 121 patients (51 with Basedow disease and 70 with Hashimoto thyroiditis), between 13 and 68 years old, with a BMI of 24.68 kg/m2 and with a female predominance (105 women). Symptoms of hyperthyroidism represented the most frequent cause of consultation. The distribution of patients regarding their thyroid disease showed that 42.1% of patients had hyperthyroidism (only one patient had subclinical hyperthyroidism), 21.5% had a subclinical hypothyroidism, 28.1% had clinical hypothyroidism and 8.3% had euthyroid goiter. Half of the patients had at least a member of their family whith a thyroid disease. The autoimmune thyroid diseases are strongly associated to other autoimmune diseases and to repetitive spontaneous abortion. Thus, 39% of the married women had had at least one spontaneous abortion and 26.4% of the patients had one or more autoimmune disease associated to their thyroid disease; diabetes mellitus type 1 representing the most frequent one. Concerning the treatment, we remarked a remission of 30 patients (66.7%) with Basedow disease after 18 months of antithyroid drug treatment of 45 patients. In Hashimoto thyroiditis, we remarked a frequent evolution of patients with subclinical hypothyroidism to overt hypothyroidism when medical treatment was not initiated.
Annals of clinical and translational neurology, Jul 25, 2022
Journal of Community Genetics, Mar 6, 2012
This study aims to investigate the association of human leukocyte antigen (HLA) class II genes an... more This study aims to investigate the association of human leukocyte antigen (HLA) class II genes and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with autoimmune thyroid diseases in the Lebanese population. A total of 128 patients with autoimmune thyroid disease (55 with Graves' disease (GD) and 73 with Hashimoto's thyroiditis (HT)) were typed for HLA DQA1 (0301 and 0501) and DQB1 (0201, 0302, and 0303) and for 49A/G CTLA-4 using PCR-based sequence-specific priming methods. A total of 186 matched controls were typed for the same alleles and compared to the diseased population. Results showed no significant differences in HLA DQB1*0201 or DQB1*0301 allelic frequencies or CTLA-4 polymorphisms between patients and controls. For GD, there was a weak association with HLA DQB1*0302 [34.6% (19 of 55) vs. 21.5% (40 of 186), P00.048, odds ratio (OR)01.926, confidence interval (CI)00.999-3.715] and HLA DQB1*0302-DQA1*0501 haplotype [56.36% (31 of 55) vs. 40.8% (76 of 186), P00.042, OR01.870, CI01.018-3.433]. For HT, the frequencies of DQB1*0302-DQA1*0501 haplotype [28.8% (21of 73) vs. 14.5% (27 of 186), P00.008, OR02.378, CI01.241-4.558] and DQB1*0302-DQA1*0301 haplotype [60.2% (44 of 73) vs. 38.7% (72 of 186), P00.002, OR02.402, CI01.381-4.180] were significantly higher in patients. On the other hand, weak association was found between HT and DQA1*0301 allele [32.9% (24 of 73) vs. 20.9% (39 of 186), P00.044, OR01.846, CI01.011-3.373]. Findings show that DQB1*0302-DQA1*0501 and DQB1*0302-DQA1*0301 haplotypes may play a role in the pathogenesis of HT in the Lebanese population. For the 49A/G CTLA-4 polymorphism, no significant difference was found between patients and controls.
Annals of Human Genetics, Dec 9, 2021
Cystic fibrosis is the most common life-limiting autosomal recessive disease in western countries... more Cystic fibrosis is the most common life-limiting autosomal recessive disease in western countries with an incidence of 1:2500 in United States and 1:1000 in some European countries. Similar incidences were noted for the Middle East with variations from 1 in 2560 to 1 in 15,876 according to the degree of consanguinity. This is a preliminary systematic study that aims to assess the incidence and carrier rate of cystic fibrosis in the Middle Eastern Lebanese population; known for a high frequency of consanguinity. One hundred thirteen DNA samples were collected from neonatal blood cards obtained from newborns to healthy unrelated families with no previous history of Cystic fibrosis. Screening for Cystic Fibrosis-causing pathogenic variants was performed using next generation sequencing, and 17 different single nucleotide variants were detected, including six pathogenic and likely pathogenic. 5.5%-7% newborns were found to be carriers of a variant strongly suggestive of pathogenicity and comparable to published literature worldwide. This pilot analysis highlights the challenging interpretation of CFTR variants in a country underrepresented by large ethnic population analyses, and stresses the importance of premarital screening programs for Cystic fibrosis.
Molecular Biology Reports
Background Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characte... more Background Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characterized by lack of pain perception with a wide spectrum of clinical signs such as anosmia and hyposmia. SCN9A gene variants were found to be associated with CIP. We here report on a family with three CIP affected patients referred for genetic investigations. Methods and Results Whole exome sequencing analysis revealed the presence of a novel nonsense, homozygous SCN9A pathogenic variant: SCN9A (NM_001365536.1): c.4633G > T, p.(Glu1545*) in exon 26. Conclusion Our three Lebanese patients had CIP, urinary incontinence and normal olfactory function while two of them also presented with osteoporosis and osteoarthritis; this association of features has not been previously reported in the literature. We hope that this report would contribute to a better delineation of the spectrum caused by SCN9A pathogenic variants.