33 results match your criteria variant bmpr1a

Implications of Splicing Alterations in the Onset and Phenotypic Variability of a Family with Subclinical Manifestation of Peutz-Jeghers Syndrome: Bioinformatic and Molecular Evidence.

Int J Mol Sci 2020 Nov 2;21(21). Epub 2020 Nov 2.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.

Peutz-Jeghers Syndrome (PJS) is an autosomal dominant pre-cancerous disorder caused in 80-90% of cases by germline mutations in the tumor suppressor gene . We performed a genetic test of the gene in two Italian young sisters suspected of PJS, since they showed pathognomonic café au lait spots in absence of other symptoms and familiarity. Sequencing of all exons of gene and other 8 genes, suggested to be involved in hamartomatous syndromes, (, , , , , , , ) led to the identification in both the probands of a novel germline silent mutation named c. Read More

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November 2020

Phenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing / Variant.

Cancer Prev Res (Phila) 2020 Oct 23. Epub 2020 Oct 23.

Hospital of the University of Pennsylvania and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Juvenile polyposis syndrome (JPS) is a clinically diagnosed hamartomatous polyposis syndrome that increases the risk of gastrointestinal cancer. Approximately 40%-50% of JPS is caused by a germline disease-causing variant (DCV) in the or genes. The aim of this study was to characterize the phenotype of DCV-negative JPS and compare it with DCV-positive JPS. Read More

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October 2020

National recommendations of the French Genetics and Cancer Group - Unicancer on the modalities of multi-genes panel analyses in hereditary predispositions to tumors of the digestive tract.

Eur J Med Genet 2020 Dec 8;63(12):104080. Epub 2020 Oct 8.

Institut Paoli-Calmettes, Department of Clinical Cancer Genetics, Aix Marseille Univ, INSERM, IRD, SESSTIM, Marseille, France.

In case of suspected hereditary predisposition to digestive cancers, next-generation sequencing can analyze simultaneously several genes associated with an increased risk of developing these tumors. Thus, "Gastro Intestinal" (GI) gene panels are commonly used in French molecular genetic laboratories. Lack of international recommendations led to disparities in the composition of these panels and in the management of patients. Read More

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December 2020

Familial juvenile polyposis syndrome with a de novo germline missense variant in BMPR1A gene: a case report.

BMC Med Genet 2020 10 8;21(1):196. Epub 2020 Oct 8.

Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Background: Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline mutations in two genes, SMAD4 and BMPR1A, have been identified to cause JPS.

Case Presentation: Here, we report a germline heterozygous missense variant (c. Read More

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October 2020

Identification of MicroRNA-Related Tumorigenesis Variants and Genes in the Cancer Genome Atlas (TCGA) Data.

Genes (Basel) 2020 08 19;11(9). Epub 2020 Aug 19.

USF Genomics & College of Public Health, University of South Florida, Tampa, FL 33612, USA.

MicroRNAs (miRNAs) are a class of small non-coding RNA that can down-regulate their targets by selectively binding to the 3' untranslated region (3'UTR) of most messenger RNAs (mRNAs) in the human genome. Single nucleotide variants (SNVs) located in miRNA target sites (MTS) can disrupt the binding of targeting miRNAs. Anti-correlated miRNA-mRNA pairs between normal and tumor tissues obtained from The Cancer Genome Atlas (TCGA) can reveal important information behind these SNVs on MTS and their associated oncogenesis. Read More

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Disease expression in juvenile polyposis syndrome: a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers.

Genet Med 2020 09 13;22(9):1524-1532. Epub 2020 May 13.

Institute for Medical Genetics and Pathology, University Hospital Basel, and Research Group Human Genomics, Department of Research, University of Basel, Basel, Switzerland.

Purpose: Juvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% of cases by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.

Methods: We performed a retrospective, questionnaire-based European multicenter survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature. Read More

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September 2020

A novel germline BMPR1A variant (c.72_73delGA) in a Japanese family with hereditary mixed polyposis syndrome.

Jpn J Clin Oncol 2020 Jul;50(7):826-829

Graduate School of Medicine, Intractable Disease Research Center, Juntendo University, Tokyo, Japan.

Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. Read More

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Homozygous missense variant in BMPR1A resulting in BMPR signaling disruption and syndromic features.

Mol Genet Genomic Med 2019 11 7;7(11):e969. Epub 2019 Sep 7.

Division of Endocrinology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, OH, USA.

Background: The bone morphogenetic protein (BMP) pathway is known to play an imperative role in bone, cartilage, and cardiac tissue formation. Truncating, heterozygous variants, and deletions of one of the essential receptors in this pathway, Bone Morphogenetic Protein Receptor Type1A (BMPR1A), have been associated with autosomal dominant juvenile polyposis. Heterozygous deletions have also been associated with cardiac and minor skeletal anomalies. Read More

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November 2019

Variable Features of Juvenile Polyposis Syndrome With Gastric Involvement Among Patients With a Large Genomic Deletion of BMPR1A.

Clin Transl Gastroenterol 2019 07;10(7):e00054

Raphael Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel.

Objectives: Loss-of-function mutations of BMPR1A cause juvenile polyposis syndrome (JPS), but large genomic deletions in BMPR1A are rare, reported in few families only, and data regarding the associated phenotype are limited.

Methods: We investigated clinical features and genomic data of 7 extended seemingly unrelated families with a genomic deletion of the entire coding region of BMPR1A. We defined mutation size, mutation prevalence, and tumor pathogenesis using whole-genome sequencing, targeted genotyping, and haplotype analysis. Read More

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Familial Left Ventricular Non-Compaction Is Associated With a Rare p.V407I Variant in Bone Morphogenetic Protein 10.

Circ J 2019 07 26;83(8):1737-1746. Epub 2019 Jun 26.

The Heart Institute, Department of Pediatrics, Cincinnati Children's Hospital Medical Center.

Background: Left ventricular non-compaction (LVNC) is a heritable cardiomyopathy characterized by hypertrabeculation, inter-trabecular recesses and thin compact myocardium, but the genetic basis and mechanisms remain unclear. This study identified novel LVNC-associated mutations inNOTCH-dependent genes and investigated their mutational effects.Methods and Results:High-resolution melting screening was performed in 230 individuals with LVNC, followed by whole exome and Sanger sequencing of available family members. Read More

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Looking for the hidden mutation: Bannayan-Riley-Ruvalcaba syndrome caused by constitutional and mosaic 10q23 microdeletions involving PTEN and BMPR1A.

Am J Med Genet A 2019 07 6;179(7):1383-1389. Epub 2019 May 6.

Department of Human Genetics, Hannover Medical School, Hannover, Germany.

The PTEN hamartoma tumor syndrome (PHTS) is caused by heterozygous germline variants in PTEN. Here, we report two unrelated patients with juvenile polyposis, macrocephaly, intellectual disability, and hyperpigmented skin macules. Both patients were clinically suspected for the Bannayan-Riley-Ruvalcaba syndrome (BRRS), a PHTS subentity. Read More

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Assessment of structurally and functionally high-risk nsSNPs impacts on human bone morphogenetic protein receptor type IA (BMPR1A) by computational approach.

Comput Biol Chem 2019 Jun 12;80:31-45. Epub 2019 Mar 12.

Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh.

BMPR1A (BMP type 1 receptor) is a transmembrane cell-surface receptor also known as ALK3 (activin-like kinases-3) encodes for a type I serine/threonine kinase receptor and a member of the transforming growth-factor β-receptor (TGF-β) super family. The BMPR1A has a significant interaction with BMP-2 for protein activity and also has a low affinity with growth and differentiation factor 5 (GDF5); positively regulates chondrocyte differentiation. The genetic variations can alter the structure and function of the BMPR1A gene that causes several diseases such as juvenile polyposis syndrome or hereditary cancer-predisposing syndrome. Read More

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A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A.

Sci Rep 2019 02 27;9(1):2959. Epub 2019 Feb 27.

Institute of Molecular Biology, Hannover Medical School, D-30625, Hannover, Germany.

The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329. Read More

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February 2019

Exome sequencing in 51 early onset non-familial CRC cases.

Mol Genet Genomic Med 2019 05 27;7(5):e605. Epub 2019 Feb 27.

Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.

Background: Colorectal cancer (CRC) cases with an age of onset <40 years suggests a germline genetic cause. In total, 51 simplex cases were included to test the hypothesis of CRC as a mendelian trait caused by either heterozygous autosomal dominant or bi-allelic autosomal recessive pathogenic variants.

Methods: The cohort was whole exome sequenced (WES) at 100× coverage. Read More

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Mga Modulates Bmpr1a Activity by Antagonizing Bs69 in Zebrafish.

Front Cell Dev Biol 2018 28;6:126. Epub 2018 Sep 28.

Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

MAX giant associated protein (MGA) is a dual transcriptional factor containing both T-box and bHLHzip DNA binding domains. studies have shown that MGA functions as a transcriptional repressor or activator to regulate transcription of promotors containing either E-box or T-box binding sites. BS69 (ZMYND11), a multidomain-containing (i. Read More

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September 2018

Optimization of the diagnosis of inherited colorectal cancer using NGS and capture of exonic and intronic sequences of panel genes.

Eur J Hum Genet 2018 11 2;26(11):1597-1602. Epub 2018 Jul 2.

Department of Genetics, F76000 and Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France.

We have developed and validated for the diagnosis of inherited colorectal cancer (CRC) a massive parallel sequencing strategy based on: (i) fast capture of exonic and intronic sequences from ten genes involved in Mendelian forms of CRC (MLH1, MSH2, MSH6, PMS2, APC, MUTYH, STK11, SMAD4, BMPR1A and PTEN); (ii) sequencing on MiSeq and NextSeq 500 Illumina platforms; (iii) a bioinformatic pipeline that includes BWA-Picard-GATK (Broad Institute) and CASAVA (Illumina) in parallel for mapping and variant calling, Alamut Batch (Interactive BioSoftware) for annotation, CANOES for CNV detection and finally, chimeric reads analysis for the detection of other types of structural variants (SVs). Analysis of 1644 new index cases allowed the identification of 323 patients with class 4 or 5 variants, corresponding to a 20% disease-causing variant detection rate. This rate reached 37% in patients with Lynch syndrome, suspected on the basis of tumour analyses. Read More

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November 2018

Cbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling.

J Exp Med 2017 Oct 16;214(10):2933-2946. Epub 2017 Aug 16.

Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

The mouse Langerhans cell (LC) network is established through the differentiation of embryonic LC precursors. BMP7 and TGFβ1 initiate cellular signaling that is essential for inducing LC differentiation and preserving LCs in a quiescent state, respectively. Here we show that loss of Cbfβ2, one of two RNA splice variants of the gene, results in long-term persistence of embryonic LC precursors after their developmental arrest at the transition into the EpCAM stage. Read More

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October 2017

Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing.

Fam Cancer 2017 04;16(2):195-203

Department of Molecular and Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups. Read More

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Hamartomatous polyps - a clinical and molecular genetic study.

Dan Med J 2016 Aug;63(8)

Hamartomatous polyps (HPs) in the gastrointestinal (GI) tract are rare compared to other types of GI polyps, yet they are the most common type of polyp in children. The symptoms are usually rectal bleeding, abdominal pain, obstipation, anaemia, and/or small bowel obstruction. The polyps are typically removed concurrently with endoscopy when located in the colon, rectum, or stomach, whereas polyps in the small bowel are removed during push-enteroscopy, device-assisted enteroscopy, or by surgery. Read More

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Genome-wide association study of platelet aggregation in African Americans.

BMC Genet 2015 May 30;16:58. Epub 2015 May 30.

Department of Medicine, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, 19107, USA.

Background: We have previously shown that platelet aggregation has higher heritability in African Americans than European Americans. However, a genome-wide association study (GWAS) of platelet aggregation in African Americans has not been reported. We measured platelet aggregation in response to arachidonic acid, ADP, collagen, or epinephrine by optical aggregometry. Read More

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Identification and functional analysis of a SLC33A1: c.339T>G (p.Ser113Arg) variant in the original SPG42 family.

Hum Mutat 2015 Feb;36(2):240-9

The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, Shandong University School of Medicine, Jinan, Shandong, 250012, China.

Using whole-exome sequencing, we surveyed all the potential pathogenic variants in an SPG42 family and found five SNPs and four indels that are shared by two patients and lie in the mapped region. Two variants, SLC33A1 p.Ser113Arg and VEPH1 p. Read More

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February 2015

A GDF5 point mutation strikes twice--causing BDA1 and SYNS2.

PLoS Genet 2013 3;9(10):e1003846. Epub 2013 Oct 3.

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany ; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité - Universitätsmedizin Berlin, Berlin, Germany.

Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. GDF5 is a susceptibility gene for osteoarthritis (OA) and mutations in GDF5 are associated with a wide variety of skeletal malformations ranging from complex syndromes such as acromesomelic chondrodysplasias to isolated forms of brachydactylies or multiple synostoses syndrome 2 (SYNS2). Here, we report on a family with an autosomal dominant inherited combination of SYNS2 and additional brachydactyly type A1 (BDA1) caused by a single point mutation in GDF5 (p. Read More

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Familial juvenile polyposis syndrome with a novel SMAD4 germline mutation.

Clin J Gastroenterol 2013 Oct 21;6(5):361-7. Epub 2013 Sep 21.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, 951-8510, Japan.

Juvenile polyposis syndrome (JPS) is a dominantly inherited disorder characterized by the development of numerous juvenile polyps (JPs) of the gastrointestinal tract, and associated with a mutation of the SMAD4 or BMPR1A gene. Here, we report a mother-daughter case of familial JPS. A 29-year-old female patient with severe iron deficiency anemia and hypoproteinemia had numerous polyps in the stomach and a few polyps in the ileum and colon that were detected endoscopically. Read More

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October 2013

Germline Mutations in the Polyposis-Associated Genes BMPR1A, SMAD4, PTEN, MUTYH and GREM1 Are Not Common in Individuals with Serrated Polyposis Syndrome.

PLoS One 2013 21;8(6):e66705. Epub 2013 Jun 21.

Cancer and Population Studies Group, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

Background: Recent reports have observed that individuals with serrated polyps, some of whom meet the clinical diagnostic criteria for Serrated Polyposis Syndrome (SPS), are among those who carry germline mutations in genes associated with polyposis syndromes including; (1) genes known to underlie hamartomatous polyposes (SMAD4, BMPR1A, and PTEN), (2) MUTYH-associated polyposis and (3) GREM1 in Hereditary Mixed Polyposis Syndrome (HMPS). The aim of this study was to characterise individuals fulfilling the current WHO criteria for SPS for germline mutations in these polyposis-associated genes.

Methods: A total of 65 individuals with SPS (fulfilling WHO criteria 1 or 3), were recruited to the Genetics of Serrated Neoplasia study between 2000 and 2012, through multiple Genetics or Family Cancer Clinics within Australia, or from the New Zealand Familial Gastrointestinal Cancer Service. Read More

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October 2017

A complex endocrine conundrum.

Fam Cancer 2013 Sep;12(3):577-80

Cellular and Molecular Medicine, St. George's University of London, London, SW17 ORE, UK,

We describe a case of recurrent primary hyperparathyroidism, manifested as 3 metachronous parathyroid adenomata, in a 50 year-old woman who also had Hashimoto hypothyroidism, gastric gastrointestinal stromal tumour (GIST), cysts in liver and kidneys, 5 intestinal polyps (one of these a villous adenoma), diverticulitis and telangiectasia of lips. She did not have medullary thyroid carcinoma (MTC). Genetic analysis of the CDC73 gene [for Hyperparathyroidism-jaw tumor (HPT-JT)], MEN1 for Multiple Endocrine Neoplasia Type1, CDKN1B for MEN4, SDHB and SDHD for Paraganglioma/Pheochromocytoma susceptibility, VHL for von Hippel-Lindau Syndrome, BMPR1A and SMAD4 for Juvenile Polyposis Syndrome (JPS) (sequencing and MLPA), karyotype and array CGH (44 K) were all normal. Read More

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September 2013

Induction of estrogen receptor α-36 expression by bone morphogenetic protein 2 in breast cancer cell lines.

Mol Med Rep 2012 Sep 12;6(3):591-6. Epub 2012 Jun 12.

Department of Biotechnology, Institute of Life Science and Biological Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China.

The expression of estrogen receptor-α (ERα) is one of the most important diagnostic and prognostic factors of breast cancer. Recently, ERα-36 has been identified as a novel variant of ER-α. ERα-36 lacks intrinsic transcription activity and mainly mediates non-genomic estrogen signaling. Read More

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September 2012

A covalently dimerized recombinant human bone morphogenetic protein-15 variant identifies bone morphogenetic protein receptor type 1B as a key cell surface receptor on ovarian granulosa cells.

Endocrinology 2012 Mar 31;153(3):1509-18. Epub 2012 Jan 31.

Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki and HUSLAB, University Central Hospital of Helsinki, FIN-00029 Helsinki, Finland.

Genetic studies have identified bone morphogenetic protein-15 (BMP15) as an essential regulator of female fertility in humans and in sheep. Oocyte-derived BMP15 is a noncovalently linked dimeric growth factor mediating its effects to ovarian somatic cells in a paracrine manner. Although receptor ectodomains capable of binding BMP15 have previously been reported, no cell surface receptor complex involved in BMP15 signaling has previously been characterized. Read More

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Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation.

Hum Mutat 2012 Apr 14;33(4):720-7. Epub 2012 Feb 14.

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.

Congenital cardiovascular malformation (CVM) exhibits familial predisposition, but most of the specific genetic factors involved are unknown. Postulating that rare variants in genes in critical cardiac developmental pathways predispose to CVM, we systematically surveyed three genes of the bone morphogenetic protein (BMP) signaling pathway for novel variants. Exonic, splice site, and untranslated regions of BMPR1A, BMPR2, and SMAD6 genes were sequenced in 90 unrelated sporadic cases of CVM. Read More

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Mouse genetic models of cleft lip with or without cleft palate.

Birth Defects Res A Clin Mol Teratol 2008 Feb;82(2):63-77

Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.

Nonsyndromic cleft lip and palate (CLP) is among the most common human birth defects. Transmission patterns suggest that the causes are "multifactorial" combinations of genetic and nongenetic factors, mostly distinct from those causing cleft secondary palate (CP). The major etiological factors are largely unknown, and the embryological mechanisms are not well understood. Read More

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February 2008