Diagnosis, surveillance, and treatment strategies for familial adenomatous polyposis

Aihara, Hiroyuki; Kumar, Nitin; Thompson, Christopher C.

doi:10.1097/meg.0000000000000010

Cited by 53 publications

(36 citation statements)

References 79 publications

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“…The remaining 10%–15% of mutations are gross deletions and duplications, which can be detected by multiplex ligation-dependent probe amplification (MLPA), Southern blot, or real-time quantitative PCR analysis. 43 – 45 …”

Section: Genetic Testing Algorithmmentioning

confidence: 99%

The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

Leoz¹,

Carballal²,

Moreira³

et al. 2015

TACG

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Familial adenomatous polyposis (FAP) is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP). FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC), and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP.

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Section: Genetic Testing Algorithmmentioning

confidence: 99%

The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

Leoz¹,

Carballal²,

Moreira³

et al. 2015

TACG

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“…Among the seven asymptomatic mutation carriers, one (III-13) is 41 years old, while the others are all under 21 years of age. 95% of individuals who have inherited an APC mutation will manifest clinical findings by age 35 years, while only 50% will have manifested findings by age 16 years (Petersen et al, 1991;Aihara et al, 2014). Thus, because of the asymptomatic 41 year old, this family displays incomplete penetrance (Evans et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes

Zhan

Wang

et al. 2020

Front. Genet.

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Background: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized primarily by the development of numerous adenomatous polyps in the colon and a high risk for colorectal cancer. FAP is caused by germline mutations of the adenomatous polyposis coli (APC) gene. The proband in this family was a 39year-old female patient with the pathologic diagnosis of adenomatous polyps, and then a five-generation kindred with FAP was characterized in the following years. This article identified an APC mutation, and demonstrated the practical use of APC-linked STR markers, which could be used to reduce misdiagnosis of prenatal diagnosis or preimplantation genetic diagnosis resulted from contamination or allele drop-out. Methods: Next-generation sequencing (NGS) was used to identify the possible APC mutations in an affected individual from a family with autosomal dominant colon cancer. Targeted sequencing then used to identify additional related individuals with the mutation. Three short tandem repeat (STR) loci, D5S299, D5S134, and D5S346, were used for PCR-based microsatellite analysis of the APC gene in the extended family. Results: We identified an APC: p.W553X mutation. The STR haplotype at the APC locus, A1B4C1, was shared by all clinically affected individuals with the APC: p.W553X mutation. In addition, the APC: p.D1822V variant was observed in 40% affected individuals and in two unaffected individuals. Conclusion: We described a protein truncation mutation, APC: p.W553X; demonstrated the value of APC-linked STR markers (D5S299, D5S134, and D5S346) haplotypes; and suggested the potential role of these haplotypes in detecting loss of heterozygosity of the APC gene.

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“…50,51 On the other hand, Bannayan-Riley-Rubacalva Syndrome, Multiple Endocrine Neoplasia type 1, Cowden syndrome and Gardner syndrome are conditions resulting from germline mutations that have concomitant lipomatosis. [52][53][54][55] Even some mutations involving mitochondrial function are related to abnormal adipose tissue growth mostly in the upper trunk and neck and the best example is the Madelung Disease. 56 However, the negative panel of AKT1, APC, MEN-1, PIK3CA, and PTEN excludes that they are responsible for the FML phenotype, at least in this research.…”

Section: Discussionmentioning

confidence: 99%

<p>Clinical and Molecular Investigation of Familial Multiple Lipomatosis: Variants in the <em>HMGA2</em> Gene</p>

Granados

Baptista

Bonadia

et al. 2020

CCID

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Background: Familial multiple lipomatosis (FML) is an autosomal dominant disorder characterized by the slow growth of encapsulated nodules spread across the trunk and limbs. Currently, there is no specific etiology; therefore, its molecular and biological bases need to be better understood. High-throughput sequencing technologies appear to be a costeffective tool and have a pivotal role in elucidating different genodermatoses.Objective: This study aimed to perform a clinical and molecular characterization of constitutional DNA of seven individuals belonging to five unrelated families diagnosed with FML. Patients and methods: Clinical aspects were obtained from medical records and physical examination. HMGA2 gene was investigated using Sanger sequencing method. Mutational analysis of other genes associated with syndromic lipomatosis AKT1, APC, PIK3CA, MEN-1, and PTEN was performed through next-generation sequencing. Results: In this series, FML was predominant among women who were overweight and reaching the age of thirty and was associated with gastrointestinal comorbidity. Histopathological diagnosis of biopsies revealed typical features of both lipoma and angiolipoma. We identified two identical novel variants with unknown significance in exon 5 of the HMGA2 gene in two participants of different families. There were no additional changes in exons 1 to 4 of the HMGA2 gene. Multi-gene panel was normal in all cases. Conclusion: Variants found in exon 5 of the HMGA2 gene have not been described and have an uncertain significance in the genesis of FML. Further studies, including a more significant number of affected individuals and functional analysis of the novel variants of HGMA2 gene, should be undertaken to better understand its biological role in FML.

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Diagnosis, surveillance, and treatment strategies for familial adenomatous polyposis

Cited by 53 publications

References 79 publications

The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes

<p>Clinical and Molecular Investigation of Familial Multiple Lipomatosis: Variants in the <em>HMGA2</em> Gene</p>

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