Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes

Bruno, Damien L.; Anderlid, Britt Marie; Wedell, Anna; Ravenswaaij-Arts, Conny M. A. van; Ganesamoorthy, Devika; Lundin, Johanna; Martin, Christa Lese; Douglas, Jessica; Nowak, C.; Adam, Margaret P; Kooy, R. Frank; Aa, Nathalie Van der; Reyniers, Edwin; Vandeweyer, Geert; Stolte‐Dijkstra, Irene; Dijkhuizen, Trijnie; Yeung, Alison; Delatycki, Martin B.; Borgström, Birgit; Thelin, Lena; Cardoso, Carlos; Bon, Bregje W.M. van; Pfundt, Rolph; Vries, Bert B.A. de; Wallin, Anders; Amor, David J.; James, Paul; Slater, Howard R.; Schoumans, Jacqueline

doi:10.1136/jmg.2009.069906

Cited by 143 publications

(201 citation statements)

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“…As the individuals described in Bruno et al 25 with hand/foot anomalies had microduplications that extended across our critical region, their limb anomalies may represent a subtle skeletal phenotype that, at the most extreme, can manifest as SHFLD. Given the decreased penetrance seen with the microduplications, there is also the possibility that a second genetic locus is involved.…”

Section: Sequence Alignments and Phylogenetic Analysismentioning

confidence: 99%

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)

Armour

Bulman

Jarinova³

et al. 2011

Eur J Hum Genet

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Split-hand/foot malformation with long-bone deficiency (SHFLD) is a relatively rare autosomal-dominant skeletal disorder, characterized by variable expressivity and incomplete penetrance. Although several chromosomal loci for SHFLD have been identified, the molecular basis and pathogenesis of most SHFLD cases are unknown. In this study we describe three unrelated kindreds, in which SHFLD segregated with distinct but overlapping duplications in 17p13.3, a region previously linked to SHFLD. In a large three-generation family, the disorder was found to segregate with a 254 kb microduplication; a second microduplication of 527 kb was identified in an affected female and her unaffected mother, and a 430 kb microduplication versus microtriplication was identified in three affected members of a multi-generational family. These findings, along with previously published data, suggest that one locus responsible for this form of SHFLD is located within a 173 kb overlapping critical region, and that the copy gains are incompletely penetrant.

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Section: Sequence Alignments and Phylogenetic Analysismentioning

confidence: 99%

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)

Armour

Bulman

Jarinova³

et al. 2011

Eur J Hum Genet

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“…5 Además, la duplicación de una región en el cromosoma 17p13.3 ha emergido como un nuevo síndrome distintivo (OMIM #613215). 9 L a s c a r a c t e r í s t i c a s f e n o t í p i c a s d e e s t e síndrome incluyen restricción del crecimiento intrauterino (RCIU), retardo del desarrollo psicomotor, hipotonía, dismorfismo craneofacial, braquidactilia, falanges distales acortadas, hallux valgus, de leve a moderado déficit cognitivo, problemas comportamentales pertenecientes a l e s p e c t r o a u t i s t a y , o c a s i o n a l m e n t e , malformaciones cerebrales que afectan el cuerpo calloso, el cerebelo y la fosa posterior. La heterogeneidad fenotípica de este síndrome es consecuencia de las variaciones de tamaño en el segmento duplicado, dadas por diferentes puntos de ruptura, que afectan el contenido génico dentro de este.…”

Section: Figura 3 Cariotipo De La Pacienteunclassified

“…Hasta el momento, han sido reportados 16 pacientes en la literatura médica indexada con duplicaciones de 17p13.3 y sus variantes. [9][10][11] Mediante el uso de la herramienta informática Genoglyphix Genome Browser de Signature Genomics, se identificaron 8 genes (Figura 4) en la región 17p13.2p13.3, correspondiente al segmento duplicado de la paciente. Uno de estos genes, CAMKK1, codifica una proteína quinasa-quinasa dependiente de calcio/calmodulina, que ha sido implicada en la transcripción génica neuronal y la plasticidad sináptica, por lo cual es posible que su sobreexpresión pueda afectar el adecuado desarrollo cerebral.…”

Section: Figura 3 Cariotipo De La Pacienteunclassified

Isocromosoma Xq en mosaico y microduplicación 17p13.3p13.2 en una paciente con síndrome de Turner y catarata congénita

Martínez

Guio

2015

Arch Argent Pediat

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Presentación de casos clínicos RESUMENLa combinación del síndrome de Turner con otros trastornos genéticos, como la catarata congénita, ha sido reportada. Sin embargo, su asociación con una forma de catarata nuclear congénita con herencia autosómica dominante y penetrancia incompleta no ha sido reportada previamente en la literatura. Tampoco existen reportes de su presentación junto con rearreglos en el cromosoma 17. A continuación, presentamos el excepcional caso de una paciente con una constelación de anomalías mayores y menores, diagnosticada con síndrome de Turner en mosaico por isocromosoma Xq, asociado a una microduplicación 17p13.3p13.2, quien además presenta catarata nuclear congénita bilateral de herencia autosómica dominante con penetrancia incompleta. Se realiza una revisión acerca del origen y la causa de estas alteraciones genéticas y una aproximación a la hipótesis de la patogénesis de la asociación de dos de estos trastornos genéticos en una misma paciente. Palabras clave: síndrome de Turner, isocromosoma Xq, catarata congénita, mosaicismo cromosómico, microduplicación 17p. ABSTRACTThe combination of Turner syndrome with other genetic disorders such as congenital cataract has been reported, but its association with a congenital form with autosomal dominant inheritance and incomplete penetrance has not been previously reported in the literature. There are no reports on its presentations with rearrangements on chromosome 17. We report the exceptional case of a 20 months old girl with a constellation of major and minor anomalies, diagnosed with mosaic Turner syndrome by isochromosome Xq associated with a microduplication 17p13.3p13.2, who also had bilateral congenital nuclear cataract autosomal dominant with incomplete penetrance. We reviewed in the literature the origin and cause of these genetic alterations and we provided an Isocromosoma Xq en mosaico y microduplicación 17p13.3p13.2 en una paciente con síndrome de Turner y catarata congénita Mosaic isochromosome Xq and microduplication 17p13.3p13.2 in a patient with Turner syndrome and congenital cataract approach to the hypothesis of the pathogenesis of the association of two of these genetic disorders in the same patient.

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“…To further investigate whether second-site variants are a distinctive feature of a subset of phenotypically variable genomic disorders, we stratified our findings in the case samples according to specific primary variants and observed a nominally significant (P<0.05) enrichment for the presence of at least one additional large variant at a second site for 7 of 72 genomic disorders (as defined by the primary variant), as compared with control samples, including the 15q11.2 (NIPA2) deletion, 12,30 16p11.2 (TBX6) duplication, 15,17 16p12.1 (CDR2) deletion, 21 16p11.2 (SH2B1) distal duplication, 3q29 (DLG1) duplication, 24 17p13.3 (YWHAE) duplication, 31 and 15q23q24 (ETFA) deletion. 1 Repeating the analysis after removal of very large copy-number variants (>30 Mb) still resulted in significance for the enrichment of second-site variants for the 7 disorders (Fig.…”

Section: Enrichment For Second-site Variantsmentioning

confidence: 99%

Phenotypic Heterogeneity of Genomic Disorders and Rare Copy-Number Variants

2012

N Engl J Med

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Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes

Cited by 143 publications

References 36 publications

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)

Isocromosoma Xq en mosaico y microduplicación 17p13.3p13.2 en una paciente con síndrome de Turner y catarata congénita

Phenotypic Heterogeneity of Genomic Disorders and Rare Copy-Number Variants

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