Duplication of <i>OCRL</i> and adjacent genes associated with autism but not Lowe syndrome

Schroer, Richard J.; Beaudet, Arthur L.; Shinawi, Marwan; Sahoo, Trilochan; Patel, Ankita; Sun, Qin; Skinner, Cindy; Stevenson, Roger E.

doi:10.1002/ajmg.a.35566

Cited by 13 publications

(9 citation statements)

References 5 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lowe syndrome, caused by sequence variants or deletions of OCRL , is characterized by early onset cataracts, depressed muscle tone and reflexes, aminoaciduria, and ID. Duplication of OCRL has been described in 3 families, all in the company of duplications of adjacent genes (Møller et al 2014; Schroer et al 2012). They have had neurodevelopmental abnormalities, ID, autism, and seizures but in no other respect has the phenotype of Lowe syndrome been seen among these boys.…”

Section: Duplication Of Xlid Of Genesmentioning

confidence: 99%

X‐linked intellectual disability update 2017

Neri

Schwartz

Lubs

et al. 2018

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

The X-chromosome comprises only about 5% of the human genome but accounts for about 15% of the genes currently known to be associated with intellectual disability. The early progress in identifying the X-linked intellectual disability (XLID)-associated genes through linkage analysis and candidate gene sequencing has been accelerated with the use of high-throughput technologies. In the 10 years since the last update, the number of genes associated with XLID has increased by 96% from 72 to 141 and duplications of all 141 XLID genes have been described, primarily through the application of high-resolution microarrays and next generation sequencing. The progress in identifying genetic and genomic alterations associated with XLID has not been matched with insights that improve the clinician's ability to form differential diagnoses, that bring into view the possibility of curative therapies for patients, or that inform scientists of the impact of the genetic alterations on cell organization and function.

show abstract

Section: Duplication Of Xlid Of Genesmentioning

confidence: 99%

X‐linked intellectual disability update 2017

Neri

Schwartz

Lubs

et al. 2018

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, a 615 Kb duplication comprising seven genes, including OCRL, was detected in a boy with autism and short stature [23]. Although both these features can also be part of the Lowe syndrome spectrum caused by deficiency of OCRL-1, they do not necessarily indicate OCRL-1 dysfunction.…”

Section: Genetic Backgroundmentioning

confidence: 99%

Lowe syndrome/Dent-2 disease: A comprehensive review of known and novel aspects

2015

View full text Add to dashboard Cite

The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, cognitive and behavioral impairment and a renal proximal tubulopathy in almost all of the patients. Whereas the ocular manifestations and severe hypotonia are present at birth, the renal involvement appears within the first months of life. Patients show progressive growth retardation and may develop a debilitating arthropathy. Treatment is symptomatic and life span rarely exceeds 40 yr. The causative OCRL gene, encodes an inositol polyphosphate 5-phosphatase. OCRL mutations were not only found in classic Lowe syndrome, but also in milder affected patients, classified as having Dent-2 disease. There is a phenotypic continuum within patients with Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of enzyme function. Researchers have conducted a large amount of work to understand the etiology responsible for the disease. However, the mechanisms leading to the clinical manifestations are still poorly understood and we are far from an effective therapy. In this review, we have included well-established findings and the most recent progress in understanding Lowe syndrome and Dent-2 disease.

show abstract

“…[1][2][3][4] Subsequent studies have used genomic microarray analysis to characterize 13 patients (8 males and 5 females) with duplications involving this region. [5][6][7][8] Male patients with Xq25q26.2 duplications are reported to have a nonspecific clinical presentation. The most frequent features include pre-and postnatal growth restriction, microcephaly, intellectual disability and learning difficulty, and a distinctive facial gestalt.…”

mentioning

confidence: 99%

Delineating the Clinical Spectrum Associated With Xq25q26.2 Duplications: Report of 2 Families and Review of the Literature

et al. 2018

View full text Add to dashboard Cite

To date, 13 patients with interstitial microduplications involving Xq25q26.2 have been reported. Here, we report 6 additional patients from 2 families with duplications involving Xq25q26.2. Family I carries a 5.3-Mb duplication involving 26 genes. This duplication was identified in 3 patients and was associated with microcephaly, growth failure, developmental delay, and dysmorphic features. Family II carries an overlapping 791-kb duplication that involves 3 genes. This duplication was identified in 3 patients and was associated with learning disability and speech delay. The size and gene content of published overlapping Xq25q26.2 duplications vary, making it difficult to define a critical region or establish a genotype-phenotype correlation. However, patients with overlapping duplications have been found to share common clinical features including microcephaly, growth failure, intellectual disability, learning difficulties, and dysmorphic features. The 2 families presented here provide additional insight into the phenotypic spectrum and clinical significance of duplications in this region.

show abstract

Duplication of OCRL and adjacent genes associated with autism but not Lowe syndrome

Cited by 13 publications

References 5 publications

X‐linked intellectual disability update 2017

X‐linked intellectual disability update 2017

Lowe syndrome/Dent-2 disease: A comprehensive review of known and novel aspects

Delineating the Clinical Spectrum Associated With Xq25q26.2 Duplications: Report of 2 Families and Review of the Literature

Contact Info

Product

Resources

About