Background: Tissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders.
Methods: Two pediatric patients with global developmental delay and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene. From independent human and murine omics datasets, we combined copy number variations, histone modifications, developmental tissue-specific regulation, and protein data to explore the molecular mechanism at play.
To date, 5 cases of 17p13.1 microduplications have been described in the literature. Intellectual disability was reported as the core feature, together with minor facial dysmorphisms and obesity, but a characteristic phenotype for 17p13.
View Article and Find Full Text PDFWhole exome sequencing (WES) is a powerful tool to identify clinically undefined forms of intellectual disability/developmental delay (ID/DD), especially in consanguineous families. Here we report the genetic definition of two sporadic cases, with syndromic ID/DD for whom array-Comparative Genomic Hybridization (aCGH) identified a de novo copy number variant (CNV) of uncertain significance. The phenotypes included microcephaly with brachycephaly and a distinctive facies in one proband, and hypotonia in the legs and mild ataxia in the other.
View Article and Find Full Text PDFAm J Med Genet B Neuropsychiatr Genet
March 2016
Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.
View Article and Find Full Text PDFBackground: Conventional karyotyping (550 bands resolution) is able to identify chromosomal aberrations >5-10 Mb, which represent a known cause of intellectual disability/developmental delay (ID/DD) and/or multiple congenital anomalies (MCA). Array-Comparative Genomic Hybridization (array-CGH) has increased the diagnostic yield of 15-20%.
Results: In a cohort of 700 ID/DD cases with or without MCA, including 15 prenatal diagnoses, we identified a subgroup of seven patients with a normal karyotype and a large complex rearrangement detected by array-CGH (at least 6, and up to 18 Mb).
We report a patient with a moderate mental retardation, afebrile seizure, mild dysmorphic features and type 2 diabetes mellitus with mild obesity and metabolic syndrome. Array-CGH analysis revealed a de novo 790-830 kb duplication on chromosome 17p13.1, not reported so far.
View Article and Find Full Text PDFWe report eight unrelated individuals with intellectual disability and overlapping submicroscopic deletions of 8q21.11 (0.66-13.
View Article and Find Full Text PDFWe describe a four-generation family in whom 5 members show the combination of a large head, ptosis, nasal speech that sometimes goes along with a cleft palate, full cheeks, small mouth, and prominent ears, and who also have learning problems. We evaluated three affected members in detail and found them to have in addition a partial cutaneous syndactyly between the third and fourth fingers, an increased distance between second and third finger, and a decreased smell. We have not been unable to find other patients described in literature with the same combination of features, and suggest this to represent a hitherto unrecognizable entity.
View Article and Find Full Text PDFBackground: Intellectual disability affects approximately 1 to 3% of the general population. The etiology is still poorly understood and it is estimated that one-half of the cases are due to genetic factors. Cryptic subtelomeric aberrations have been found in roughly 5 to 7% of all cases.
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