Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

A Novel Mutation in the VPS13B Gene in a Cohen Syndrome Patient with Positive Antiphospholipid Antibodies

A Novel Mutation in the VPS13B Gene in a Cohen Syndrome Patient with Positive Antiphospholipid... Hindawi Case Reports in Immunology Volume 2021, Article ID 3143609, 3 pages https://doi.org/10.1155/2021/3143609 Case Report A Novel Mutation in the VPS13B Gene in a Cohen Syndrome Patient with Positive Antiphospholipid Antibodies 1 2 3 1,4,5 Roghayeh Dehghan , Mahdiyeh Behnam, Alireza Moafi, and Mansoor Salehi Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Pediatric Hematology and Oncology, Isfahan University of Medical Sciences, Isfahan, Iran Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran Correspondence should be addressed to Mansoor Salehi; m_salehi@med.mui.ac.ir Received 2 July 2021; Accepted 16 August 2021; Published 26 August 2021 Academic Editor: Elena Bozzola Copyright © 2021 Roghayeh Dehghan et al. (is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cohen syndrome is an autosomal recessive disorder with the primary symptoms of mental deficiency, progressive retinopathy, hypotonia, microcephaly, obesity of midchildhood onset, intermittent neutropenia, and dysmorphic facial features. (e syndrome has high phenotypic heterogeneity and is caused by loss-of-function mutations in the VPS13B gene. Here, we introduce a novel homozygous nonsense mutation (c.8698G> T, p.E2900X) in the VPS13B gene in an 11-year-old Iranian boy with major symptoms of Cohen syndrome. He also had mild anemia accompanied by positive antiphospholipid antibodies, the latter has never been previously reported in Cohen syndrome. and the intracellular transport of proteins [4–7]. However, it 1. Introduction is not clear how and through which cellular pathways Cohen syndrome is an autosomal recessive disorder that was VPS13B mutations lead to multisystemic symptoms of first described by Cohen in 1973. (e authors reported three Cohen syndrome. (e identification and study of novel Finnish cases with hypotonia, obesity of midchildhood mutations could broaden our knowledge on the association onset, mental deficiency, and ocular-cranial anomalies [1]. between different symptoms of Cohen syndrome and dif- Neutropenia was later identified as another continuous ferent functional motifs of the VPS13B gene. (is knowledge symptom of the disease, and the discovery of over 100 could, in turn, help further elucidate the cellular functions cases worldwide revealed Cohen syndrome to have high and pathways of VPS13B in organs involved in the pathology phenotypic heterogeneity, particularly in non-Finnish of Cohen syndrome. patients [2, 3]. In the present case-report study, we introduce a case of In 2003, Cohen syndrome was shown to be caused by Cohen syndrome with a novel homozygous nonsense mu- loss-of-function mutations in the gene VPS13B (also known tation (c.8698 G> T, p.E2900X) in exon 48 of the VPS13B as COH1; 4). (is large gene, containing 62 exons, encodes a gene. (is case, in addition to the common major symptoms peripheral membrane protein composed of several domains of the syndrome, also presented with positive anti- and functional motifs. Cellular and molecular studies have phospholipid antibodies (APAs), which have not been shown that VPS13B is involved in vesicle-mediated sorting previously reported in Cohen syndrome to date. 2 Case Reports in Immunology 2. Case Presentation 3. Discussion 2.1. Clinical Studies. An 11-year-old Iranian boy with Cohen syndrome is a genetic disorder with high phenotypic syndromic obesity was referred to the Medical Genetics variability and primary symptoms of mental deficiency, Centre of Genome (Isfahan, Iran) for genetic analysis. (e progressive retinopathy, hypotonia, microcephaly, obesity of child had mild mental retardation, hyperactivity, and midchildhood onset, intermittent neutropenia, and dys- progressive visual impairment, with signs of retinal pig- morphic facial features [3]. (is case report describes the mentary changes and waxy pale optic discs in eye exami- case of an 11-year-old boy who presented with typical nation. (e patient had truncal obesity, long slender symptoms of Cohen syndrome, as well as persistent mild extremities, and joint hyperlaxity at the time of referral. anemia. In addition, serological tests revealed that the pa- According to his medical documents, although the child had tient had been positive for anticardiolipin and anti-β2- a normal head circumference at birth, he began to develop glycoprotein 1 IgGs since the age of six when he was first microcephaly at the age of one. In addition, the patient had a tested for antiphospholipid syndrome (APS) following a history of developmental milestones, such as making his first thrombocytopenic bleeding complication. APS is an auto- steps later than is normal at age 19 months. His facial immune disease characterized by the detection of circulating features included hypertelorism, thick eyebrows, thick APAs and arterial/venous thrombosis. It is associated with bushy hair, a low hairline, and a short upper lip. (e patient recurrent miscarriage in pregnant women and thrombo- had been having frequent colds since infancy, and his cytopenia in some patients [8]. APS can occur primarily, complete blood count showed persistent moderate neu- without association with other diseases or secondarily to tropenia and mild anemia, with an absolute neutrophil other autoimmune disorders, such as SLE and rheumatoid count (ANC) of 600 cells/uL and a hemoglobin level of arthritis. Medical examinations and records had ruled out 11.8 g/dL in his last hematological test at the time of referral. the APS-related autoimmune disorders in our patient, and At age six, the child experienced thrombocytopenia-asso- he had never experienced arterial/venous thrombosis. ciated bleeding with a very low platelet count of 21,000/uL. To the best of our knowledge, to date, no study has However, the platelet count was in the normal range in evaluated the APS and APAs in Cohen syndrome. However, further follow-up CBC tests. Following the aforementioned there is one report of thrombocytopenia in a male patient thrombocytopenic bleeding, antiphospholipid antibodies with a homozygous deletion of the first eight exons of the were evaluated, and the patient was found to be positive for VPS13B gene [9, 10]. Interestingly, thrombocytopenia with 9 −1 9 −1 two main APAs: anticardiolipin IgG and anti-β2-glyco- a platelet count below<100 ×10 L and<150 ×10 L has protein 1 IgG, with a titration of 23.7 and 300.2 U/mL, been reported in 20% and 53% of APS patients, respectively, respectively, in his last APA test at age 11. However, the which has led to bleeding complications in rare cases patient was negative for lupus anticoagulant and antinuclear [11, 12]. In addition, thrombosis, a main clinical manifes- antibodies (ANAs), and clinical examination ruled out tation of APS, has been reported in two siblings affected with systemic lupus erythematosus (SLE) and rheumatoid ar- symptoms of Cohen syndrome. Laboratory tests revealed a thritis, which are two suspected underlying autoimmune combined deficiency of protein C, protein S, and anti- diseases for positive antiphospholipid antibodies. thrombin III in these siblings, while their APAs were not (e proband was the only child of healthy consan- evaluated [13]. Some studies have shown an interaction guineous parents (first cousin), and similar symptoms had between APAs with coagulation proteins, such as protein C; not been reported in any of his first- or second-degree for this reason, we suspect an underlying role of these relatives. (ese criteria suggested that he has an autosomal antibodies in the coagulation defects reported in these recessive genetic disorder. Cohen syndrome, in particular, siblings [14]. was suspected based on his symptoms, and after obtaining (e positive APAs in our patient, as well as two previous informed consent of the parents, whole-exome sequencing reports of thrombocytopenia and thrombosis in Cohen was performed for genetic diagnosis. syndrome, raise several questions. Could mutations in the VPS13B gene drive APA in some cases of Cohen syndrome? If so, could APAs contribute to rare instances of throm- 2.2. Genetic Studies. Genomic DNA was extracted from the bocytopenia or thrombosis in Cohen syndrome? To answer proband’s peripheral blood and subjected to clinical these questions, it is necessary to study the medical history of whole-exome sequencing at a depth of 100X on an Illu- thrombocytopenia and thrombosis in more cases of Cohen mina HiSeq 4000. Sequence data were aligned to the syndrome and evaluate the platelet count and APAs in these human reference genome (GRCh38) using the Bur- cases. (ese evaluations, beyond their research value, could rows–Wheeler Alignment Tool. Variants were called using also aid in risk assessments and in preventing hematological the Genome Analysis Tool Kit and annotated using complications in Cohen patients. ANNOVAR. We detected a homozygous nonsense variant In this case report, in addition to reporting a new (c.8698 G> T, p.E2900X) in exon 48 of the VPS13 B gene pathogenic mutation in the VPS13B gene, we described and confirmed the homozygosity of the patient and positive APAs in a patient with Cohen syndrome for the first time. Future studies could investigate the relationship be- heterozygosity of his parents for the variant using Sanger sequencing (Figure 1). tween Cohen syndrome and APAs and explore whether Case Reports in Immunology 3 (c.8698G>T, p.E2900X) I-1 I-2 I-3 I-4 III-3 .. 103 = 1 base II-1 II-2 II-3 II-4 II-5 II-6 II-7 III-2 III-1 III-2 III-3 III-4 III-5 2 .. 162 = 1 base IV-1 IV-2 IV-1 11 y 5 y confirmed Down syndrome Figure 1: Sanger sequencing confirmed the homozygosity of the patient and heterozygosity of his parents for c.8698 G> T, p.E2900X in the VPS13B gene. these antibodies could be the underlying cause of rare in- [6] K. Redding, J. H. Brickner, L. G. Marschall, J. W. Nichols, and R. S. Fuller, “Allele-specific suppression of a defective trans- stances of thrombocytopenia or coagulation disorders in Golgi network (TGN) localization signal in Kex2p identifies Cohen syndrome. Given that APAs can cause serious issues three genes involved in localization of TGN transmembrane such as thrombosis and bleeding complications, they should proteins,” Molecular and Cellular Biology, vol. 16, no. 11, be evaluated as a precautionary measure in Cohen patients. pp. 6208–6217, 1996. [7] J. H. Brickner and R. S. Fuller., “SOI1 encodes a novel, Data Availability conserved protein that promotes TGN-endosomal cycling of Kex2p and other membrane proteins by modulating the Sequencing results are available for the case on request. function of two TGN localization signals,” Journal of Cell Biology, vol. 139, no. 1, pp. 23–36, 1997. [8] K. Schreiber, S Sciascia, P. G de Groot et al., “Anti- Conflicts of Interest phospholipid syndrome,” Nature reviews. Disease primers, (e authors have no conflicts of interest to declare. vol. 4, no. 1, pp. 17103–17120, 2018. [9] T. J. De Ravel, K. Dillen, and J. P. Fryns, “A new association of mental retardation, short stature, unusual face, radio-ulnar References synostosis and retinal pigment abnormalities: Cohen syn- [1] M. M. Cohen, B. D Hall, D. W Smith, C. B Graham, and drome with thrombocytopenia,” Genetic Counseling, vol. 13, K. J Lampert, “A new syndrome with hypotonia, obesity, no. 4, pp. 475-476, 2002. [10] I. Balikova, A.-E. Lehesjoki, T. J. L. de Ravel et al., “Deletions mental deficiency, and facial, oral, ocular, and limb anoma- lies,” ,e Journal of Pediatrics, vol. 83, no. 2, pp. 280–284, in theVPS13B(COH1) gene as a cause of Cohen syndrome,” Human Mutation, vol. 30, no. 9, pp. E845–E854, 2009. [2] R. Norio, C. Raitta, and E. Lindahl, “Further delineation of the [11] E. Pontara, A. Banzato, E. Bison et al., “(rombocytopenia in high-risk patients with antiphospholipid syndrome,” Journal Cohen syndrome; report on chorioretinal dystrophy, leuko- penia and consanguinity,” Clinical Genetics, vol. 25, no. 1, of ,rombosis and Haemostasis, vol. 16, no. 3, pp. 529–532, pp. 1–14, 1984. [3] J. M. Rodrigues, H. D Fernandes, C Caruthers, S. R Braddock, [12] R. Cervera, M. Tektonidou, G. Espinosa et al., “Task force on catastrophic antiphospholipid syndrome (APS) and non- and A. P Knutsen, “Cohen syndrome: review of the literature,” Cureus, vol. 10, p. e3330, 2018. criteria APS manifestations (II): thrombocytopenia and [4] J. Kolehmainen, G. C. M. Black, A. Saarinen et al., “Cohen skin manifestations,” Lupus, vol. 20, no. 2, pp. 174–181, syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in [13] T. L. Schlichtemeier, G. E Tomlinson, B. A Kamen, L. J Waber, and G. N Wilson, “Multiple coagulation defects and the cohen vesicle-mediated sorting and intracellular protein transport,” ,e American Journal of Human Genetics, vol. 72, no. 6, syndrome,” Clinical Genetics, vol. 45, no. 4, pp. 212–216, 1994. [14] D. Wahl, A. Membre, C. Perret-Guillaume, V. Regnault, and pp. 1359–1369, 2003. [5] A. Velayos-Baeza, A. Vettori, R. R. Copley, C. Dobson-Stone, T. Lecompte, “Mechanisms of antiphospholipid-induced thrombosis: effects on the protein C system,” Current and A. P. Monaco, “Analysis of the human VPS13 gene family,” Genomics, vol. 84, no. 3, pp. 536–549, 2004. Rheumatology Reports, vol. 11, no. 1, pp. 77–81, 2009. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Immunology Hindawi Publishing Corporation

A Novel Mutation in the VPS13B Gene in a Cohen Syndrome Patient with Positive Antiphospholipid Antibodies

Loading next page...
 
/lp/hindawi-publishing-corporation/a-novel-mutation-in-the-vps13b-gene-in-a-cohen-syndrome-patient-with-cIuOWuQal3
Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2021 Roghayeh Dehghan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
2090-6609
eISSN
2090-6617
DOI
10.1155/2021/3143609
Publisher site
See Article on Publisher Site

Abstract

Hindawi Case Reports in Immunology Volume 2021, Article ID 3143609, 3 pages https://doi.org/10.1155/2021/3143609 Case Report A Novel Mutation in the VPS13B Gene in a Cohen Syndrome Patient with Positive Antiphospholipid Antibodies 1 2 3 1,4,5 Roghayeh Dehghan , Mahdiyeh Behnam, Alireza Moafi, and Mansoor Salehi Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Pediatric Hematology and Oncology, Isfahan University of Medical Sciences, Isfahan, Iran Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran Correspondence should be addressed to Mansoor Salehi; m_salehi@med.mui.ac.ir Received 2 July 2021; Accepted 16 August 2021; Published 26 August 2021 Academic Editor: Elena Bozzola Copyright © 2021 Roghayeh Dehghan et al. (is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cohen syndrome is an autosomal recessive disorder with the primary symptoms of mental deficiency, progressive retinopathy, hypotonia, microcephaly, obesity of midchildhood onset, intermittent neutropenia, and dysmorphic facial features. (e syndrome has high phenotypic heterogeneity and is caused by loss-of-function mutations in the VPS13B gene. Here, we introduce a novel homozygous nonsense mutation (c.8698G> T, p.E2900X) in the VPS13B gene in an 11-year-old Iranian boy with major symptoms of Cohen syndrome. He also had mild anemia accompanied by positive antiphospholipid antibodies, the latter has never been previously reported in Cohen syndrome. and the intracellular transport of proteins [4–7]. However, it 1. Introduction is not clear how and through which cellular pathways Cohen syndrome is an autosomal recessive disorder that was VPS13B mutations lead to multisystemic symptoms of first described by Cohen in 1973. (e authors reported three Cohen syndrome. (e identification and study of novel Finnish cases with hypotonia, obesity of midchildhood mutations could broaden our knowledge on the association onset, mental deficiency, and ocular-cranial anomalies [1]. between different symptoms of Cohen syndrome and dif- Neutropenia was later identified as another continuous ferent functional motifs of the VPS13B gene. (is knowledge symptom of the disease, and the discovery of over 100 could, in turn, help further elucidate the cellular functions cases worldwide revealed Cohen syndrome to have high and pathways of VPS13B in organs involved in the pathology phenotypic heterogeneity, particularly in non-Finnish of Cohen syndrome. patients [2, 3]. In the present case-report study, we introduce a case of In 2003, Cohen syndrome was shown to be caused by Cohen syndrome with a novel homozygous nonsense mu- loss-of-function mutations in the gene VPS13B (also known tation (c.8698 G> T, p.E2900X) in exon 48 of the VPS13B as COH1; 4). (is large gene, containing 62 exons, encodes a gene. (is case, in addition to the common major symptoms peripheral membrane protein composed of several domains of the syndrome, also presented with positive anti- and functional motifs. Cellular and molecular studies have phospholipid antibodies (APAs), which have not been shown that VPS13B is involved in vesicle-mediated sorting previously reported in Cohen syndrome to date. 2 Case Reports in Immunology 2. Case Presentation 3. Discussion 2.1. Clinical Studies. An 11-year-old Iranian boy with Cohen syndrome is a genetic disorder with high phenotypic syndromic obesity was referred to the Medical Genetics variability and primary symptoms of mental deficiency, Centre of Genome (Isfahan, Iran) for genetic analysis. (e progressive retinopathy, hypotonia, microcephaly, obesity of child had mild mental retardation, hyperactivity, and midchildhood onset, intermittent neutropenia, and dys- progressive visual impairment, with signs of retinal pig- morphic facial features [3]. (is case report describes the mentary changes and waxy pale optic discs in eye exami- case of an 11-year-old boy who presented with typical nation. (e patient had truncal obesity, long slender symptoms of Cohen syndrome, as well as persistent mild extremities, and joint hyperlaxity at the time of referral. anemia. In addition, serological tests revealed that the pa- According to his medical documents, although the child had tient had been positive for anticardiolipin and anti-β2- a normal head circumference at birth, he began to develop glycoprotein 1 IgGs since the age of six when he was first microcephaly at the age of one. In addition, the patient had a tested for antiphospholipid syndrome (APS) following a history of developmental milestones, such as making his first thrombocytopenic bleeding complication. APS is an auto- steps later than is normal at age 19 months. His facial immune disease characterized by the detection of circulating features included hypertelorism, thick eyebrows, thick APAs and arterial/venous thrombosis. It is associated with bushy hair, a low hairline, and a short upper lip. (e patient recurrent miscarriage in pregnant women and thrombo- had been having frequent colds since infancy, and his cytopenia in some patients [8]. APS can occur primarily, complete blood count showed persistent moderate neu- without association with other diseases or secondarily to tropenia and mild anemia, with an absolute neutrophil other autoimmune disorders, such as SLE and rheumatoid count (ANC) of 600 cells/uL and a hemoglobin level of arthritis. Medical examinations and records had ruled out 11.8 g/dL in his last hematological test at the time of referral. the APS-related autoimmune disorders in our patient, and At age six, the child experienced thrombocytopenia-asso- he had never experienced arterial/venous thrombosis. ciated bleeding with a very low platelet count of 21,000/uL. To the best of our knowledge, to date, no study has However, the platelet count was in the normal range in evaluated the APS and APAs in Cohen syndrome. However, further follow-up CBC tests. Following the aforementioned there is one report of thrombocytopenia in a male patient thrombocytopenic bleeding, antiphospholipid antibodies with a homozygous deletion of the first eight exons of the were evaluated, and the patient was found to be positive for VPS13B gene [9, 10]. Interestingly, thrombocytopenia with 9 −1 9 −1 two main APAs: anticardiolipin IgG and anti-β2-glyco- a platelet count below<100 ×10 L and<150 ×10 L has protein 1 IgG, with a titration of 23.7 and 300.2 U/mL, been reported in 20% and 53% of APS patients, respectively, respectively, in his last APA test at age 11. However, the which has led to bleeding complications in rare cases patient was negative for lupus anticoagulant and antinuclear [11, 12]. In addition, thrombosis, a main clinical manifes- antibodies (ANAs), and clinical examination ruled out tation of APS, has been reported in two siblings affected with systemic lupus erythematosus (SLE) and rheumatoid ar- symptoms of Cohen syndrome. Laboratory tests revealed a thritis, which are two suspected underlying autoimmune combined deficiency of protein C, protein S, and anti- diseases for positive antiphospholipid antibodies. thrombin III in these siblings, while their APAs were not (e proband was the only child of healthy consan- evaluated [13]. Some studies have shown an interaction guineous parents (first cousin), and similar symptoms had between APAs with coagulation proteins, such as protein C; not been reported in any of his first- or second-degree for this reason, we suspect an underlying role of these relatives. (ese criteria suggested that he has an autosomal antibodies in the coagulation defects reported in these recessive genetic disorder. Cohen syndrome, in particular, siblings [14]. was suspected based on his symptoms, and after obtaining (e positive APAs in our patient, as well as two previous informed consent of the parents, whole-exome sequencing reports of thrombocytopenia and thrombosis in Cohen was performed for genetic diagnosis. syndrome, raise several questions. Could mutations in the VPS13B gene drive APA in some cases of Cohen syndrome? If so, could APAs contribute to rare instances of throm- 2.2. Genetic Studies. Genomic DNA was extracted from the bocytopenia or thrombosis in Cohen syndrome? To answer proband’s peripheral blood and subjected to clinical these questions, it is necessary to study the medical history of whole-exome sequencing at a depth of 100X on an Illu- thrombocytopenia and thrombosis in more cases of Cohen mina HiSeq 4000. Sequence data were aligned to the syndrome and evaluate the platelet count and APAs in these human reference genome (GRCh38) using the Bur- cases. (ese evaluations, beyond their research value, could rows–Wheeler Alignment Tool. Variants were called using also aid in risk assessments and in preventing hematological the Genome Analysis Tool Kit and annotated using complications in Cohen patients. ANNOVAR. We detected a homozygous nonsense variant In this case report, in addition to reporting a new (c.8698 G> T, p.E2900X) in exon 48 of the VPS13 B gene pathogenic mutation in the VPS13B gene, we described and confirmed the homozygosity of the patient and positive APAs in a patient with Cohen syndrome for the first time. Future studies could investigate the relationship be- heterozygosity of his parents for the variant using Sanger sequencing (Figure 1). tween Cohen syndrome and APAs and explore whether Case Reports in Immunology 3 (c.8698G>T, p.E2900X) I-1 I-2 I-3 I-4 III-3 .. 103 = 1 base II-1 II-2 II-3 II-4 II-5 II-6 II-7 III-2 III-1 III-2 III-3 III-4 III-5 2 .. 162 = 1 base IV-1 IV-2 IV-1 11 y 5 y confirmed Down syndrome Figure 1: Sanger sequencing confirmed the homozygosity of the patient and heterozygosity of his parents for c.8698 G> T, p.E2900X in the VPS13B gene. these antibodies could be the underlying cause of rare in- [6] K. Redding, J. H. Brickner, L. G. Marschall, J. W. Nichols, and R. S. Fuller, “Allele-specific suppression of a defective trans- stances of thrombocytopenia or coagulation disorders in Golgi network (TGN) localization signal in Kex2p identifies Cohen syndrome. Given that APAs can cause serious issues three genes involved in localization of TGN transmembrane such as thrombosis and bleeding complications, they should proteins,” Molecular and Cellular Biology, vol. 16, no. 11, be evaluated as a precautionary measure in Cohen patients. pp. 6208–6217, 1996. [7] J. H. Brickner and R. S. Fuller., “SOI1 encodes a novel, Data Availability conserved protein that promotes TGN-endosomal cycling of Kex2p and other membrane proteins by modulating the Sequencing results are available for the case on request. function of two TGN localization signals,” Journal of Cell Biology, vol. 139, no. 1, pp. 23–36, 1997. [8] K. Schreiber, S Sciascia, P. G de Groot et al., “Anti- Conflicts of Interest phospholipid syndrome,” Nature reviews. Disease primers, (e authors have no conflicts of interest to declare. vol. 4, no. 1, pp. 17103–17120, 2018. [9] T. J. De Ravel, K. Dillen, and J. P. Fryns, “A new association of mental retardation, short stature, unusual face, radio-ulnar References synostosis and retinal pigment abnormalities: Cohen syn- [1] M. M. Cohen, B. D Hall, D. W Smith, C. B Graham, and drome with thrombocytopenia,” Genetic Counseling, vol. 13, K. J Lampert, “A new syndrome with hypotonia, obesity, no. 4, pp. 475-476, 2002. [10] I. Balikova, A.-E. Lehesjoki, T. J. L. de Ravel et al., “Deletions mental deficiency, and facial, oral, ocular, and limb anoma- lies,” ,e Journal of Pediatrics, vol. 83, no. 2, pp. 280–284, in theVPS13B(COH1) gene as a cause of Cohen syndrome,” Human Mutation, vol. 30, no. 9, pp. E845–E854, 2009. [2] R. Norio, C. Raitta, and E. Lindahl, “Further delineation of the [11] E. Pontara, A. Banzato, E. Bison et al., “(rombocytopenia in high-risk patients with antiphospholipid syndrome,” Journal Cohen syndrome; report on chorioretinal dystrophy, leuko- penia and consanguinity,” Clinical Genetics, vol. 25, no. 1, of ,rombosis and Haemostasis, vol. 16, no. 3, pp. 529–532, pp. 1–14, 1984. [3] J. M. Rodrigues, H. D Fernandes, C Caruthers, S. R Braddock, [12] R. Cervera, M. Tektonidou, G. Espinosa et al., “Task force on catastrophic antiphospholipid syndrome (APS) and non- and A. P Knutsen, “Cohen syndrome: review of the literature,” Cureus, vol. 10, p. e3330, 2018. criteria APS manifestations (II): thrombocytopenia and [4] J. Kolehmainen, G. C. M. Black, A. Saarinen et al., “Cohen skin manifestations,” Lupus, vol. 20, no. 2, pp. 174–181, syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in [13] T. L. Schlichtemeier, G. E Tomlinson, B. A Kamen, L. J Waber, and G. N Wilson, “Multiple coagulation defects and the cohen vesicle-mediated sorting and intracellular protein transport,” ,e American Journal of Human Genetics, vol. 72, no. 6, syndrome,” Clinical Genetics, vol. 45, no. 4, pp. 212–216, 1994. [14] D. Wahl, A. Membre, C. Perret-Guillaume, V. Regnault, and pp. 1359–1369, 2003. [5] A. Velayos-Baeza, A. Vettori, R. R. Copley, C. Dobson-Stone, T. Lecompte, “Mechanisms of antiphospholipid-induced thrombosis: effects on the protein C system,” Current and A. P. Monaco, “Analysis of the human VPS13 gene family,” Genomics, vol. 84, no. 3, pp. 536–549, 2004. Rheumatology Reports, vol. 11, no. 1, pp. 77–81, 2009.

Journal

Case Reports in ImmunologyHindawi Publishing Corporation

Published: Aug 26, 2021

References