Neural tube defects and the 13q deletion syndrome: Evidence for a critical region in 13q33-34

Luo, Jeffrey; Balkin, Nancy; Stewart, Julie F.; Sarwark, John F.; Charrow, Joel; Nye, Jeffrey S.

doi:10.1002/(sici)1096-8628(20000320)91:3<227::aid-ajmg14>3.0.co;2-i

Cited by 49 publications

(30 citation statements)

References 20 publications

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“…We showed a strong association with anencephaly for 13q22-q34 (P < 0.0001). Brown et al (1993) deWned a critical region in 13q32; however, Luo et al (2000) questioned this Wnding and suggested deletion in 13q33-q34 as suYcient to cause an NTD. ZIC2 and ZIC5 are considered strong candidate genes for neural tube defects.…”

Section: Discussionmentioning

confidence: 58%

Chromosomal map of human brain malformations

Tyshchenko

Lurie²,

Schinzel

2008

Hum Genet

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The etiology of most central nervous system (CNS) malformations remains unknown. We have utilized the fact that autosomal chromosome aberrations are commonly associated with CNS malformations to identify new causative gene loci. The human cytogenetic database, a computerized catalog of the clinical phenotypes associated with cytogenetically detectable human chromosome aberrations, was used to identify patients with 14 selected brain malformations including 541 with deletions, and 290 carrying duplications. These cases were used to develop an autosomal deletion and duplication map consisting of 67 different deleted malformation associated bands (MABs) in 55 regions and 88 different duplicated MABs in 36 regions; 31 of the deleted and 8 duplicated MABs were highly significantly associated (P < 0.001). All holoprosencephaly MABs found in the database contained a known HPE gene providing some level of validation for the approach. Significantly associated MABs are discussed for each malformation together with the published data about known disease-causing genes and reported malformation-associated loci, as well as the limitations of the proposed approach.

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Section: Discussionmentioning

confidence: 58%

Chromosomal map of human brain malformations

Tyshchenko

Lurie²,

Schinzel

2008

Hum Genet

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“…Polymorphisms in these genes, however, are not significantly associated with NTDs in all populations, suggesting that polygenic and environmental factors are important. Our groups and others have described NTDs in chromosomal and inherited syndromes, including trisomy 13 (13)(14)(15)(16), trisomy 18 (16 -19), trisomy 21, and 22q11.2 and 13q deletion syndromes (20)(21)(22)(23). In rare cases, syndromes that variably present with NTDs have been associated with a mutation in a single gene (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36).…”

Section: Introductionmentioning

confidence: 99%

“…During mouse embryogenesis, high levels of Glypican 5 are expressed in the neural tube (72). Consistent with a potential role of glypicans in spina bifida, patients with 13q deletions that sometimes remove GPC5 and GPC6 can present with NTDs (23,73). Collectively, these results implicate the glypican gene family in promoting normal neural tube development.…”

Section: Introductionmentioning

confidence: 99%

Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene

Bassuk

Muthuswamy

Boland³

et al. 2012

Human Molecular Genetics

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Neural tube defects (NTDs) are common birth defects of complex etiology. Family and population-based studies have confirmed a genetic component to NTDs. However, despite more than three decades of research, the genes involved in human NTDs remain largely unknown. We tested the hypothesis that rare copy number variants (CNVs), especially de novo germline CNVs, are a significant risk factor for NTDs. We used array-based comparative genomic hybridization (aCGH) to identify rare CNVs in 128 Caucasian and 61 Hispanic patients with non-syndromic lumbar-sacral myelomeningocele. We also performed aCGH analysis on the parents of affected individuals with rare CNVs where parental DNA was available (42 sets). Among the eight de novo CNVs that we identified, three generated copy number changes of entire genes. One large heterozygous deletion removed 27 genes, including PAX3, a known spina bifida-associated gene. A second CNV altered genes (PGPD8, ZC3H6) for which little is known regarding function or expression. A third heterozygous deletion removed GPC5 and part of GPC6, genes encoding glypicans. Glypicans are proteoglycans that modulate the activity of morphogens such as Sonic Hedgehog (SHH) and bone morphogenetic proteins (BMPs), both of which have been implicated in NTDs. Additionally, glypicans function in the planar cell polarity (PCP) pathway, and several PCP genes have been associated with NTDs. Here, we show that GPC5 orthologs are expressed in the neural tube, and that inhibiting their expression in frog and fish embryos results in NTDs. These results implicate GPC5 as a gene required for normal neural tube development.

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“…We next extended our CGHa analysis to patients who had been reported as having 13q-syndrome which involves various partial deletions in the q22-qter region (Luo et al, 2000;Gutierrez et al, 2001;Hewson and Carter, 2002). These patients have a well-defined set of clinical phenotypes, including mental retardation, where the deletion was generally assumed to involve the terminal region of 13q, although somatic cell hybrid studies (Hawthorn and Cowell, 1995) suggested that these were, in fact, subterminal deletions.…”

Section: Resultsmentioning

confidence: 99%