Genetic backgrounds and diagnosis of familial hypercholesterolemia
Clin Genet. 2023 Oct 17. doi: 10.1111/cge.14435. Online ahead of print.ABSTRACTLipid disorders play a critical role in the intricate development of atherosclerosis and its clinical consequences, such as coronary heart disease and stroke. These disorders are responsible for a significant number of deaths in many adult populations worldwide. Familial hypercholesterolemia (FH) is a genetic disorder that causes extremely high levels of LDL cholesterol. The most common mutations occur in genes responsible for low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK...
Source: Clinical Genetics - October 18, 2023 Category: Genetics & Stem Cells Authors: Joanna Rogozik Renata G łówczyńska Marcin Grabowski Source Type: research
Variants in DOK7 results in fetal akinesia deformation sequence: A case report and review of literature
We report the third case of FADS due to biallelic DOK7 variants, which further strengthens the association of DOK7 with this lethal phenotype and lack of genotype phenotype correlation.PMID:37849383 | DOI:10.1111/cge.14431 (Source: Clinical Genetics)
Source: Clinical Genetics - October 18, 2023 Category: Genetics & Stem Cells Authors: Amit K Tiwari Varunvenkat M Srinivasan Shubha R Phadke Deepti Saxena Source Type: research
Adding to the evidence of gene-disease association of RAP1B and syndromic thrombocytopenia
Clin Genet. 2023 Oct 18. doi: 10.1111/cge.14438. Online ahead of print.ABSTRACTSyndromic constitutive thrombocytopenia encompasses a heterogeneous group of disorders characterised by quantitative and qualitative defects of platelets while featuring other malformations. Recently, heterozygous, de novo variants in RAP1B were reported in three cases of syndromic thrombocytopenia. Here, we report two additional, unrelated individuals identified retrospectively in our data repository with heterozygous variants in RAP1B: NM_001010942.2(RAP1B):c.35G>A, p.(Gly12Glu) (de novo) and NM_001010942.2(RAP1B):c.178G>A, p.(Gly60Arg)....
Source: Clinical Genetics - October 18, 2023 Category: Genetics & Stem Cells Authors: Luba M Pardo Ruxandra Aanicai Emir Zonic Anna H Hakonen Susan Zielske Peter Bauer Aida M Bertoli-Avella Source Type: research
A homozygous frameshift variant expands the clinical spectrum of SAMD9 gene defects
Clin Genet. 2023 Oct 13. doi: 10.1111/cge.14439. Online ahead of print.ABSTRACTSAMD9, a ubiquitously expressed protein, is involved in several mechanisms, including endosome fusion, growth suppression and modulation of innate immune responses to stress and viral infections. While biallelic mutations in SAMD9 are linked to normophosphatemic familial tumoral calcinosis, heterozygous gain-of-function mutations in the same gene are responsible for MIRAGE, a multisystemic syndrome characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. A two-and-a-half-year-old...
Source: Clinical Genetics - October 13, 2023 Category: Genetics & Stem Cells Authors: Cybel Mehawej Maroun Ibrahim Lynn Khalife Eliane Chouery Setrida El Hachem Alain Sayad Aya El Traboulsi Adlette Inati Andre Megarbane Source Type: research
A homozygous frameshift variant expands the clinical spectrum of SAMD9 gene defects
Clin Genet. 2023 Oct 13. doi: 10.1111/cge.14439. Online ahead of print.ABSTRACTSAMD9, a ubiquitously expressed protein, is involved in several mechanisms, including endosome fusion, growth suppression and modulation of innate immune responses to stress and viral infections. While biallelic mutations in SAMD9 are linked to normophosphatemic familial tumoral calcinosis, heterozygous gain-of-function mutations in the same gene are responsible for MIRAGE, a multisystemic syndrome characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. A two-and-a-half-year-old...
Source: Clinical Genetics - October 13, 2023 Category: Genetics & Stem Cells Authors: Cybel Mehawej Maroun Ibrahim Lynn Khalife Eliane Chouery Setrida El Hachem Alain Sayad Aya El Traboulsi Adlette Inati Andre Megarbane Source Type: research
A homozygous frameshift variant expands the clinical spectrum of SAMD9 gene defects
Clin Genet. 2023 Oct 13. doi: 10.1111/cge.14439. Online ahead of print.ABSTRACTSAMD9, a ubiquitously expressed protein, is involved in several mechanisms, including endosome fusion, growth suppression and modulation of innate immune responses to stress and viral infections. While biallelic mutations in SAMD9 are linked to normophosphatemic familial tumoral calcinosis, heterozygous gain-of-function mutations in the same gene are responsible for MIRAGE, a multisystemic syndrome characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. A two-and-a-half-year-old...
Source: Clinical Genetics - October 13, 2023 Category: Genetics & Stem Cells Authors: Cybel Mehawej Maroun Ibrahim Lynn Khalife Eliane Chouery Setrida El Hachem Alain Sayad Aya El Traboulsi Adlette Inati Andre Megarbane Source Type: research
A homozygous frameshift variant expands the clinical spectrum of SAMD9 gene defects
Clin Genet. 2023 Oct 13. doi: 10.1111/cge.14439. Online ahead of print.ABSTRACTSAMD9, a ubiquitously expressed protein, is involved in several mechanisms, including endosome fusion, growth suppression and modulation of innate immune responses to stress and viral infections. While biallelic mutations in SAMD9 are linked to normophosphatemic familial tumoral calcinosis, heterozygous gain-of-function mutations in the same gene are responsible for MIRAGE, a multisystemic syndrome characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. A two-and-a-half-year-old...
Source: Clinical Genetics - October 13, 2023 Category: Genetics & Stem Cells Authors: Cybel Mehawej Maroun Ibrahim Lynn Khalife Eliane Chouery Setrida El Hachem Alain Sayad Aya El Traboulsi Adlette Inati Andre Megarbane Source Type: research
A homozygous frameshift variant expands the clinical spectrum of SAMD9 gene defects
Clin Genet. 2023 Oct 13. doi: 10.1111/cge.14439. Online ahead of print.ABSTRACTSAMD9, a ubiquitously expressed protein, is involved in several mechanisms, including endosome fusion, growth suppression and modulation of innate immune responses to stress and viral infections. While biallelic mutations in SAMD9 are linked to normophosphatemic familial tumoral calcinosis, heterozygous gain-of-function mutations in the same gene are responsible for MIRAGE, a multisystemic syndrome characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. A two-and-a-half-year-old...
Source: Clinical Genetics - October 13, 2023 Category: Genetics & Stem Cells Authors: Cybel Mehawej Maroun Ibrahim Lynn Khalife Eliane Chouery Setrida El Hachem Alain Sayad Aya El Traboulsi Adlette Inati Andre Megarbane Source Type: research
Exploring factors impacting haplotype-based noninvasive prenatal diagnosis for single-gene recessive disorders
Clin Genet. 2023 Oct 11. doi: 10.1111/cge.14434. Online ahead of print.ABSTRACTHaplotype-based noninvasive prenatal diagnosis (NIPD) is applicable for various recessive single-gene disorders in proband families. However, a comprehensive exploration of critical factors influencing the assay performance, such as fetal fraction, informative single nucleotide polymorphism (SNP) count, and recombination events, has yet to be performed. It is critical to identify key factors affecting NIPD performance, including its accuracy and success rate, and their impact on clinical diagnostics to guide clinical practice. We conducted a pro...
Source: Clinical Genetics - October 12, 2023 Category: Genetics & Stem Cells Authors: Lingrong Kong Shaojun Li Zhenhua Zhao Jun Feng Xinyu Fu Huanyun Li Jingqi Zhu Yanan Wang Weiqin Tang Chao Yuan Feifei Li Xiujuan Han Di Wu Xiangdong Kong Luming Sun Source Type: research
A novel non-recurrent CNV deletion involving TBX4 and leaving TBX2 intact causes congenital alveolar dysplasia
Clin Genet. 2023 Oct 11. doi: 10.1111/cge.14428. Online ahead of print.ABSTRACTCongenital alveolar dysplasia (CAD) belongs to rare lethal lung developmental disorders (LLDDs) in neonates, manifesting with acute respiratory failure and pulmonary arterial hypertension refractory to treatment. The majority of CAD cases have been associated with copy-number variant (CNV) deletions at 17q23.1q23.2 or 5p12. Most CNV deletions at 17q23.1q23.2 were recurrent and encompassed two closely located genes, TBX4 and TBX2. In a few CAD cases, intragenic frameshifting deletions or single-nucleotide variants (SNVs) involved TBX4 but not TBX...
Source: Clinical Genetics - October 11, 2023 Category: Genetics & Stem Cells Authors: Katarzyna Bzd ęga Mateusz Biela Gail H Deutsch Joseph A Kitzmiller Ma łgorzata Rydzanicz Rafa ł Płoski Jeffrey A Whitsett Robert Śmigiel Justyna A Karolak Source Type: research
A novel non-recurrent CNV deletion involving TBX4 and leaving TBX2 intact causes congenital alveolar dysplasia
Clin Genet. 2023 Oct 11. doi: 10.1111/cge.14428. Online ahead of print.ABSTRACTCongenital alveolar dysplasia (CAD) belongs to rare lethal lung developmental disorders (LLDDs) in neonates, manifesting with acute respiratory failure and pulmonary arterial hypertension refractory to treatment. The majority of CAD cases have been associated with copy-number variant (CNV) deletions at 17q23.1q23.2 or 5p12. Most CNV deletions at 17q23.1q23.2 were recurrent and encompassed two closely located genes, TBX4 and TBX2. In a few CAD cases, intragenic frameshifting deletions or single-nucleotide variants (SNVs) involved TBX4 but not TBX...
Source: Clinical Genetics - October 11, 2023 Category: Genetics & Stem Cells Authors: Katarzyna Bzd ęga Mateusz Biela Gail H Deutsch Joseph A Kitzmiller Ma łgorzata Rydzanicz Rafa ł Płoski Jeffrey A Whitsett Robert Śmigiel Justyna A Karolak Source Type: research
CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews
Clin Genet. 2023 Oct 9. doi: 10.1111/cge.14432. Online ahead of print.ABSTRACTNeonatal ichthyosis and sclerosing cholangitis syndrome (NISCH), also known as ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC), is an extremely rare disease of autosomal recessive inheritance, resulting from loss of function of the tight junction protein claudin-1. Its clinical presentation is highly variable, and is characterized by liver and ectodermal involvement. Although most ILVASC cases described to date were attributed to homozygous truncating variants in CLDN1, a single missense variant CLDN1 p.Arg81His, ass...
Source: Clinical Genetics - October 10, 2023 Category: Genetics & Stem Cells Authors: Marina Eskin-Schwartz Vadim Dolgin Elena Didkovsky Ilana Aminov Anna Pikovsky Noam Hadar Eyal Kristal Galina Ling Idan Cohen Uri Zilberman Ohad S Birk Source Type: research
CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews
Clin Genet. 2023 Oct 9. doi: 10.1111/cge.14432. Online ahead of print.ABSTRACTNeonatal ichthyosis and sclerosing cholangitis syndrome (NISCH), also known as ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC), is an extremely rare disease of autosomal recessive inheritance, resulting from loss of function of the tight junction protein claudin-1. Its clinical presentation is highly variable, and is characterized by liver and ectodermal involvement. Although most ILVASC cases described to date were attributed to homozygous truncating variants in CLDN1, a single missense variant CLDN1 p.Arg81His, ass...
Source: Clinical Genetics - October 10, 2023 Category: Genetics & Stem Cells Authors: Marina Eskin-Schwartz Vadim Dolgin Elena Didkovsky Ilana Aminov Anna Pikovsky Noam Hadar Eyal Kristal Galina Ling Idan Cohen Uri Zilberman Ohad S Birk Source Type: research
LRRC23 deficiency causes male infertility with idiopathic asthenozoospermia by disrupting the assembly of radial spokes
This study provides strong preliminary evidence that LRRC23 defects are potential causative factors of AZS in humans, which expands our knowledge for improved genetic counseling and better reproductive recommendations for patients with AZS.PMID:37804054 | DOI:10.1111/cge.14433 (Source: Clinical Genetics)
Source: Clinical Genetics - October 7, 2023 Category: Genetics & Stem Cells Authors: Yuqian Li Qiang Zhang Qing Tan Xuan Sha Yang Gao Rong Hua Ping Zhou Zhaolian Wei Xiaojin He Yunxia Cao Tao Li Huan Wu Source Type: research
LRRC23 deficiency causes male infertility with idiopathic asthenozoospermia by disrupting the assembly of radial spokes
This study provides strong preliminary evidence that LRRC23 defects are potential causative factors of AZS in humans, which expands our knowledge for improved genetic counseling and better reproductive recommendations for patients with AZS.PMID:37804054 | DOI:10.1111/cge.14433 (Source: Clinical Genetics)
Source: Clinical Genetics - October 7, 2023 Category: Genetics & Stem Cells Authors: Yuqian Li Qiang Zhang Qing Tan Xuan Sha Yang Gao Rong Hua Ping Zhou Zhaolian Wei Xiaojin He Yunxia Cao Tao Li Huan Wu Source Type: research
