We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4.One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included.Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM.MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.

10.1200/jco.2005.08.034

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Citations (145)

Deletion of the OPHN1 gene detected by aCGH

Journal of Intellectual Disability Research (2007)

Irene Madrigal Laia Rodríguez‐Revenga Célia Bádenas Aurora Sánchez Montserrat Milà

The oligophrenin 1 gene (OPHN1) is an Rho-GTPase-activating protein involved in the regulation of the G-protein cycle required for dendritic spine morphogenesis. Mutations in this gene are implicated in X-linked mental retardation (XLMR).We report a deletion spanning exons 21 and 22 of the OPHN1 gene identified by a tiling path X-chromosome array comparative genomic hybridization (CGH) and multiplex ligation-dependent probe amplification, confirmed by polymerase chain reaction (PCR), in a family with four males with intellectual disabilities.Patients harbouring mutations in this gene share the same clinical manifestations reinforcing the idea of a syndromic XLMR. The most important neurological findings are cerebellar hypoplasia and ventriculomegaly.We recommend screening of the OPHN1 gene in male patients with XLMR and cerebellar anomalies. This case highlights the value of high-resolution techniques as Multiplex Ligation Probe Amplification (MLPA) and CGH array for a better characterization of copy number changes and suggests that MLPA technology may be very useful for an initial screening of small deletions and duplications in XLMR patients.

Cerebellar hypoplasia (non-human)

Gene dosage

Comparative genomic hybridization

10.1111/j.1365-2788.2007.00997.x

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Citations (16)

Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients

American Journal of Kidney Diseases (2000)

Roser Torrá Célia Bádenas Laureano Pérez-Oller José Luís San Millán

PKD1

Nonsense mutation

10.1053/ajkd.2000.17619

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Citations (50)

Reply to He et al

European Journal of Human Genetics (2010)

Judit García-Villoria Laura Gort Irene Madrigal Carme Fons Cristina Fernández

10.1038/ejhg.2010.194

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Citations (2)

Associated features in females with an FMR1 premutation

Journal of Neurodevelopmental Disorders (2014)

Anne Wheeler Donald B. Bailey Elizabeth Berry‐Kravis Jan S. Greenberg Molly Losh

Changes in the fragile X mental retardation 1 gene (FMR1) have been associated with specific phenotypes, most specifically those of fragile X syndrome (FXS), fragile X tremor/ataxia syndrome (FXTAS), and fragile X primary ovarian insufficiency (FXPOI). Evidence of increased risk for additional medical, psychiatric, and cognitive features and conditions is now known to exist for individuals with a premutation, although some features have been more thoroughly studied than others. This review highlights the literature on medical, reproductive, cognitive, and psychiatric features, primarily in females, that have been suggested to be associated with changes in the FMR1 gene. Based on this review, each feature is evaluated with regard to the strength of evidence of association with the premutation. Areas of need for additional focused research and possible intervention strategies are suggested.

Fragile X Syndrome

FMR1

10.1186/1866-1955-6-30

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Citations (125)

Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers

The Cerebellum (2016)

Deborah A. Hall Erin Robertson Annie L. Shelton Molly Losh Montserrat Milà

FMR1

Penetrance

Fragile X Syndrome

Intention tremor