Redefining the Etiologic Landscape of Cerebellar Malformations.

Cerebellar malformations are diverse congenital anomalies frequently associated with developmental disability. Although genetic and prenatal non-genetic causes have been described, no systematic analysis has been performed. Here, we present a large-exome sequencing study of Dandy-Walker malformation (DWM) and cerebellar hypoplasia (CBLH).

Genotype-phenotype analysis of 4q deletion syndrome: proposal of a critical region.

Chromosome 4q deletion syndrome (4q- syndrome) is a rare condition, with an estimated incidence of 1 in 100,000. Although variable, the clinical spectrum commonly includes craniofacial, developmental, digital, skeletal, and cardiac involvement. Data on the genotype-phenotype correlation within the 4q arm are limited.

Detection of pathogenic copy number variants in children with idiopathic intellectual disability using 500 K SNP array genomic hybridization.

Background: Array genomic hybridization is being used clinically to detect pathogenic copy number variants in children with intellectual disability and other birth defects. However, there is no agreement regarding the kind of array, the distribution of probes across the genome, or the resolution that is most appropriate for clinical use.

Results: We performed 500 K Affymetrix GeneChip array genomic hybridization in 100 idiopathic intellectual disability trios, each comprised of a child with intellectual disability of unknown cause and both unaffected parents.

Characterization of a new X-linked mental retardation syndrome with microcephaly, cortical malformation, and thin habitus.

X-linked mental retardation (XLMR) affects 1-2/1,000 males and accounts for approximately 10% of all mental retardation (MR). We have ascertained a syndromic form of XLMR segregating within a five-generation family with seven affected males. Prominent characteristics include mild to severe MR, cortical malformation, microcephaly, seizures, thin build with distinct facial features including a long and thin face, epicanthic folds, almond-shaped eyes, upslanting palpebral fissures and micrognathia and behavioral problems.

The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies.

Down syndrome (DS), or trisomy 21, is a common disorder associated with several complex clinical phenotypes. Although several hypotheses have been put forward, it is unclear as to whether particular gene loci on chromosome 21 (HSA21) are sufficient to cause DS and its associated features. Here we present a high-resolution genetic map of DS phenotypes based on an analysis of 30 subjects carrying rare segmental trisomies of various regions of HSA21.

The 12q14 microdeletion syndrome: additional patients and further evidence that HMGA2 is an important genetic determinant for human height.

Characteristic features of the 12q14 microdeletion syndrome include low birth weight, failure to thrive, short stature, learning disabilities and Buschke-Ollendorff lesions in bone and skin. This report on two additional patients with this microdeletion syndrome emphasizes the rather constant and uniform phenotype encountered in this disorder and refines the critical region to a 2.61 Mb interval on 12q14.

Osteopoikilosis, short stature and mental retardation as key features of a new microdeletion syndrome on 12q14.

This report presents the detection of a heterozygous deletion at chromosome 12q14 in three unrelated patients with a similar phenotype consisting of mild mental retardation, failure to thrive in infancy, proportionate short stature and osteopoikilosis as the most characteristic features. In each case, this interstitial deletion was found using molecular karyotyping. The deletion occurred as a de novo event and varied between 3.

Pregnancy with uterine vascular malformations associated with hemorrhagic hereditary telangiectasia: a case report.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant condition. It is rarely seen in pregnancy and even more rarely has uterine manifestations.

Case: A 29-year-old primigravid woman with HHT was noted to have vascular manifestations of her disease in the lower uterus, distal rectum, pelvis, and bladder before pregnancy.

Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation.

The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically detectable chromosomal abnormalities are the most frequently recognized cause, but gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy-number variants.

Unusual segregation products in sperm from a pericentric inversion 17 heterozygote.

Chromosome segregation and interchromosomal effect were studied in spermatozoa from a carrier of a pericentric chromosome 17 inversion, 46,XY,inv(17)(p13.1q25.3).

Implications of the age range in a population-based BRCA1 testing program with eligibility based on family history of breast and ovarian cancer.

The current options available to BRCA1 mutation carriers can be classified as either cancer risk reduction or increased disease surveillance. Risk reduction might be preferable to young women. Increased surveillance might be more attractive to women when their cancer risk is highest.