Hydrocephaly, penoscrotal transposition, and digital anomalies associated with de novo pseudodicentric rearranged chromosome 13 characterized by classical cytogenetic methods and mBAND analysis

Christofolini, Denise Maria; Yoshimoto, Maisa; Squire, Jeremy A.; Brunoni, Décio; Melaragno, Maria Isabel; Carvalheira, Gianna

doi:10.1002/ajmg.a.31269

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…3). An association of identical hand and foot malformations has been consistently found previously in individuals with 13q deletion patients [Tranebjaerg et al, 1988; Brown et al, 1995; Gutierrez et al, 2001; Amor et al, 2005; Kasyan and Benirschke, 2005; Christofolini et al, 2006], but not frequently in persons with normal karyotype. Based on these observations we suggest the described distal limb anomalies association to be considered as a separate entity different from the pure thumb a‐/hypoplasia and specific for 13q deletions.…”

Section: Discussionsupporting

confidence: 53%

“…The association of anal atresia with penoscrotal transposition and hypospadias has an entry in the catalog of Mendelian Inheritance in Man (OMIM #602553). It is mainly confined to persons with deletions of 13q [Carmichael et al, 1977; Vittu et al, 1989; Brown et al, 1993; Bartsch et al, 1996; Christofolini et al, 2006]. Bartsch et al 1996 found the chromosomal region 13q32.2q34 to be critical for such an association, and Garcia et al 2006 has further narrowed down this region to an approximately 9.5‐Mb interval of 13q33.3–q34 delineated by markers D13S280–D13S285.…”

Section: Discussionmentioning

confidence: 99%

“…Although individuals with 13q deletions present with a wide phenotypic spectrum, a pattern of common dysmorphic features and malformations has emerged. It includes micro‐/brachy‐/trigonocephaly, meningocele/encephalocele, anencephaly, Dandy–Walker malformation, holoprosencephaly, microphthalmia, coloboma of the retina, cleft lip/palate, thumb a‐/hypoplasia, digital anomalies, talipes, lung hypoplasia, intestinal malrotation, Hirschsprung's disease, bowel atresia, ambiguous genitalia, penoscrotal transposition with anal atresia, as well as moderate to severe mental and growth retardation [Tranebjaerg et al, 1988; Brown et al, 1993; Brewer et al, 1998; Gutierrez et al, 2001; Alanay et al, 2005; Christofolini et al, 2006; Ballarati et al, 2007; Walczak‐Sztulpa et al, 2008]. There are limited data about the dysmorphic profile of partial 13q monosomies.…”

Section: Introductionmentioning

confidence: 99%

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Phenotype and 244k array‐CGH characterization of chromosome 13q deletions: An update of the phenotypic map of 13q21.1‐qter

Kirchhoff

Bisgaard

Stoeva

et al. 2009

American J of Med Genetics Pt A

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Partial deletions of the long arm of chromosome 13 lead to variable phenotypes dependant on the size and position of the deleted region. In order to update the phenotypic map of chromosome 13q21.1-qter deletions, we applied 244k Agilent oligonucleotide-based array-CGH to determine the exact breakpoints in 14 patients with partial deletions of this region. Subsequently, we linked the genotype to the patient's phenotype. Using this approach, we were able to refine the smallest deletion region linked to short stature (13q31.3: 89.5-91.6 Mb), microcephaly (13q33.3-q34), cortical development malformations (13q33.1-qter), Dandy-Walker malformation (DWM) (13q32.2-q33.1), corpus callosum agenesis (CCA) (13q32.3-q33.1), meningocele/encephalocele (13q31.3-qter), DWM, CCA, and neural tube defects (NTDs) taken together (13q32.3-q33.1), ano-/microphthalmia (13q31.3-13qter), cleft lip/palate (13q31.3-13q33.1), lung hypoplasia (13q31.3-13q33.1), and thumb a-/hypoplasia (13q31.3-q33.1 and 13q33.3-q34). Based on observations of this study and previous reports we suggest a new entity, "distal limb anomalies association," linked to 13q31.3q33.1 segment. Most of the individuals with deletion of any part of 13q21qter showed surprisingly similar facial dysmorphic features, and thus, a "13q deletion facial appearance" was suggested. Prominent nasal columella was mapped between 13q31.3 and 13q33.3, and micrognathia between 13q21.33 and 13q31.1. The degree of mental delay did not display a particular phenotype-genotype correlation on chromosome 13. In contrast to previous reports of carriers of 13q32 band deletions as the most seriously affected patients, we present two such individuals with long-term survival, 28 and 2.5 years.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phenotype and 244k array‐CGH characterization of chromosome 13q deletions: An update of the phenotypic map of 13q21.1‐qter

Kirchhoff

Bisgaard

Stoeva

et al. 2009

American J of Med Genetics Pt A

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“…4,13,30,[38][39][40][41][42][43][44] Thus, analysis of the precise location and size of the deletion is needed to better inform families and physicians about the clinical expectations and survival in patients with a 13q deletion.…”

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confidence: 99%

Genotype–phenotype correlations in patients with retinoblastoma and interstitial 13q deletions

et al. 2011

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Patients with an interstitial 13q deletion that contains the RB1 gene show retinoblastoma and variable clinical features. Relationship between phenotypic expression and loss of specific neighboring genes are unresolved, yet. We obtained clinical, cytogenetic and molecular data in 63 patients with an interstitial 13q deletion involving RB1. Whole-genome array analysis or customized high-resolution array analysis for 13q14.11q14.3 was performed in 38 patients, and cytogenetic analysis was performed in 54 patients. Deletion sizes ranged between 4.2 kb and more than 33.43 Mb; breakpoints were non-recurrent. Sequence analysis of deletion junctions in five patients revealed microhomology and insertion of 2-34 base pairs suggestive of non-homologous end joining. Milder phenotypic expression of retinoblastoma was observed in patients with deletions larger than 1 Mb, which contained the MED4 gene. Clinical features were compared between patients with small (within 13q14), medium (within 13q12.3q21.2) and large (within 13q12q31.2) deletions. Patients with a small deletion can show macrocephaly, tall stature, obesity, motor and/or speech delay. Patients with a medium deletion show characteristic facial features, mild to moderate psychomotor delay, short stature and microcephaly. Patients with a large deletion have characteristic craniofacial dysmorphism, short stature, microcephaly, mild to severe psychomotor delay, hypotonia, constipation and feeding problems. Additional features included deafness, seizures and brain and heart anomalies. We found no correlation between clinical features and parental origin of the deletion. Our data suggest that hemizygous loss of NUFIP1 and PCDH8 may contribute to psychomotor delay, deletion of MTLR1 to microcephaly and loss of EDNRB to feeding difficulties and deafness.

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“…Individuals with 13q partial deletion present with a wide phenotypic spectrum which includes intellectual disability; growth delay; minor facial dysmorphic features; major malformations involving the brain, renal, heart, genital, and gastrointestinal systems; eye anomalies such as retinoblastoma, and distal limb abnormalities [Brown et al, 1993;Van Buggenhout et al, 1999;Alanay et al, 2005;Christofolini et al, 2006;Ballarati et al, 2007;Walczak-Sztulpa et al, 2008]. Brown et al [1993] classified the patients with 13q deletion in 3 groups: (1) those with proximal deletions, usually not extending into 13q32, presenting with mild or moderate intellectual disability, variable minor anomalies, growth delay, and sometimes, retinoblastoma; (2) those with more distal deletions, including at least part of 13q32, with severe intellectual disability, growth delay, microcephaly, and brain, eye, gastrointestinal tract, and distal limb abnormalities, and (3) those with the most distal deletions, involving 13q33q34, presenting with severe intellectual disability but without other major malformations or growth delay.…”

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confidence: 99%

Deletion of Chromosome 13 due to Different Rearrangements and Impact on Phenotype

et al. 2019

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Patients with deletion of chromosome 13 present with variable clinical features, and the correlation between phenotype and genomic aberration is not well established in the literature, mainly due to variable sizes of the deleted segments and inaccuracy of breakpoint mapping. In order to improve the genotype-phenotype correlation, we obtained clinical and cytogenomic data from 5 Brazilian patients with different chromosome 13 deletions characterized by G-banding and array techniques. Breakpoints were nonrecurrent, with deletion sizes ranging from 3.8 to 43.3 Mb. Our patients showed some classic features associated with 13q deletion, independent of the location and size of the deletion: hypotonia, growth delay, psychomotor developmental delay, microcephaly, central nervous system anomalies, and minor facial dysmorphism as well as urogenital and limb abnormalities. Comparisons between the literature and our patients' data allowed us to narrow the critical regions that were previously reported for microphthalmia and urogenital abnormalities, indicating that gene haploinsufficiency of ARHGEF7, PCDH9 and DIAPH3, of MIR17HG and GPC6, and of EFNB2 may contribute to microcephaly, cardiovascular disease, and urogenital abnormalities, respectively. The knowledge about genes involved in the phenotypic features found in 13q deletion patients may help us to understand how the genes interact and contribute to their clinical phenotype, improving the patient's clinical follow-up.

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Hydrocephaly, penoscrotal transposition, and digital anomalies associated with de novo pseudodicentric rearranged chromosome 13 characterized by classical cytogenetic methods and mBAND analysis

Cited by 8 publications

References 30 publications

Phenotype and 244k array‐CGH characterization of chromosome 13q deletions: An update of the phenotypic map of 13q21.1‐qter

Phenotype and 244k array‐CGH characterization of chromosome 13q deletions: An update of the phenotypic map of 13q21.1‐qter

Genotype–phenotype correlations in patients with retinoblastoma and interstitial 13q deletions

Deletion of Chromosome 13 due to Different Rearrangements and Impact on Phenotype

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