A genome-wide association analysis of chromosomal aberrations and Hirschsprung disease

Bae, Joon Seol; Koh, In Song; Cheong, Hyun Sub; Seo, Jeong Meen; Kim, Dae Yeon; Oh, Jung Tak; Kim, Sujeong; Jung, Kyuwhan; Sul, Jae Hoon; Park, Woong-Yang; Kim, Jeong Hyun; Shin, Hyoung Doo

doi:10.1016/j.trsl.2016.06.001

Cited by 11 publications

(8 citation statements)

References 16 publications

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“…We have performed a high density custom array-CGH to search for DNA copy imbalances at selected candidate genes and loci in a total of 59 HSCR patients. Despite our interest on the RET gene, we could not detect any novel variant at this locus, in line with what reported by others [16–18, 25, 32]. Moreover, the RET locus presented with false positive calls, confirming the difficulties raised by this subcentromeric region.…”

Section: Discussionsupporting

confidence: 89%

“…Only six CNVs overlapped with known HSCR loci, none involving the RET gene [17]. Another study investigated 123 HSCR patients and 432 unaffected subjects, with Illumina’s HumanOmni1-Quad BeadChip, finding 16 CNV regions associated with HSCR [18]. Finally, very recently, Tilghman et al (2019) have dissected, through both karyotyping and exome sequencing, the differential contribution to HSCR development of three different molecular classes of risk alleles, namely rare coding variants, common non coding variants and large CNVs and chromosomal anomalies.…”

Section: Introductionmentioning

confidence: 99%

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Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

Lantieri

Gimelli

Viaggi

et al. 2019

Orphanet J Rare Dis

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BackgroundHirschsprung Disease (HSCR) is a congenital defect of the intestinal innervations characterized by complex inheritance. Many susceptibility genes including RET, the major HSCR gene, and several linked regions and associated loci have been shown to contribute to disease pathogenesis. Nonetheless, a proportion of patients still remains unexplained. Copy Number Variations (CNVs) have already been involved in HSCR, and for this reason we performed Comparative Genomic Hybridization (CGH), using a custom array with high density probes.ResultsA total of 20 HSCR candidate regions/genes was tested in 55 sporadic patients and four patients with already known chromosomal aberrations. Among 83 calls, 12 variants were experimentally validated, three of which involving the HSCR crucial genes SEMA3A/3D, NRG1, and PHOX2B. Conversely RET involvement in HSCR does not seem to rely on the presence of CNVs while, interestingly, several gains and losses did co-occur with another RET defect, thus confirming that more than one predisposing event is necessary for HSCR to develop. New loci were also shown to be involved, such as ALDH1A2, already found to play a major role in the enteric nervous system. Finally, all the inherited CNVs were of maternal origin.ConclusionsOur results confirm a wide genetic heterogeneity in HSCR occurrence and support a role of candidate genes in expression regulation and cell signaling, thus contributing to depict further the molecular complexity of the genomic regions involved in the Enteric Nervous System development. The observed maternal transmission bias for HSCR associated CNVs supports the hypothesis that in females these variants might be more tolerated, requiring additional alterations to develop HSCR disease.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

Lantieri

Gimelli

Viaggi

et al. 2019

Orphanet J Rare Dis

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“…For analysis of aneuploidy or CNVs, the microarray scanning results were processed using the B allele frequency and Log R ratio, and the core algorithm was according to the cnvPartition as reported. 35 , 36 For chromosome rearrangements, the molecular karyotype of an unbalanced embryo could help to pinpoint the relatively accurate breakpoints positions, and informative SNPs of 2 Mbp region around the breakpoints were focused upon to establish haplotypes. When no unbalanced embryo was identified, the breakpoints from the peripheral blood karyotype were used, and the range used for linkage analysis extended to 5‐10 Mb.…”

Section: Methodsmentioning

confidence: 99%

A comprehensive and universal approach for embryo testing in patients with different genetic disorders

Zhang

Chen

et al. 2021

Clinical & Translational Med

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“…Comúnmente vista como un desorden genético, ya que el Mendelismo no siempre está presente; actualmente existen bases patogénicas y genéticas que hablan de los aspectos de esta enfermedad, incluyendo la descripción y relación de alrededor de 13 genes en la morfogénesis y diferenciación del sistema nervioso entérico (Rebollar et al, 2016). Actualmente, la mutación más importante se localiza en el RET (Bae et al, 2016; (protooncogén localizado en el brazo largo del cromosoma 10), con detección arriba del 50% en los casos con familiares relacionados a la enfermedad de Hirschsprung y arriba del 20% en casos esporádicos (Rebollar et al, 2016). Asimismo, se ha visto la susceptibilidad de la enfermedad en las variantes de los loci de SEMA3 y NRG1 para esta enfermedad .…”

Section: Materiales Y Métodosunclassified

Enfermedad de Hirschsprung en un paciente adulto: reporte de un caso en el Hospital Central del Estado de Chihuahua, México

Sánchez¹,

Gallegos

Santiesteban³

et al. 2018

TECNOCIENCIA Chih.

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Introducción. La enfermedad de Hirschsprung descrita por Harald Hirschsprung en 1888 es una patología rara (1/5,000 nacidos vivos) presentándose comúnmente como una obstrucción intestinal en el recién nacido. Enfermedad caracterizada por la ausencia de células ganglionares en el plexo de Auerbach e hipertrofia de los troncos nerviosos relacionados. Incidencia de 1 en cada 5,000 nacimientos vivos, con predominancia en hombres 4:1. En el adulto las manifestaciones incluyen una historia de estreñimiento crónico en los casos leves y perforación del colon en su presentación más grave. Justificación. Patología rara en el adulto con pocos casos reportados en la literatura global. Objetivo. Documentar caso clínico con revisión bibliográfica. Material y métodos. Reporte de caso. Discusión. En nuestro caso, el diagnóstico fue ratificado histopatológicamente hasta los 21 años de edad. Se incluye a los poco más de 300 casos de enfermedad de Hirschsprung en el adulto o adolescentes que han sido reportados en la literatura. Conclusión. La enfermedad de Hirschsprung en el adulto es una patología extremadamente poco común, pero no por eso debemos dejar de sospecharla en pacientes con ciertas características. DOI: https://doi.org/10.54167/tch.v12i1.127

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A genome-wide association analysis of chromosomal aberrations and Hirschsprung disease

Cited by 11 publications

References 16 publications

Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

A comprehensive and universal approach for embryo testing in patients with different genetic disorders

Enfermedad de Hirschsprung en un paciente adulto: reporte de un caso en el Hospital Central del Estado de Chihuahua, México

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