Somatic mosaicism for the p.His1047Arg mutation in PIK3CA in a girl with mesenteric lipomatosis.

We describe a patient who presented with a localized growth of mature fat tissue, which was surgically removed. MRI imaging identified diffuse increase in visceral adipose tissue. Targeted deep sequencing of the resected tissue uncovered a p.

Precocious puberty in two girls with PEHO syndrome: a clinical feature not previously described.

The authors present 2 girls with progressive encephalopathy, hypsarrhythmia, and optic atrophy syndrome. They describe a novel finding, precocious puberty, a feature not previously reported in this syndrome. The authors also present their clinical features and the results of investigations, including radiological findings, and compare the patients of this report to previously reported cases.

Pseudohypoparathyroidism type 1a and the GNAS p.R231H mutation: Somatic mosaicism in a mother with two affected sons.

Pseudohypoparathyrodism (PHP) is a disorder caused by mutations in the guanine nucleotide-binding α-subunit (GNAS). We sought to determine the genetic origin of PHP1a in one affected family. We identified the previously reported Gsα R231H mutation in family members affected with PHP1a.

Methylation profiling in individuals with Russell-Silver syndrome.

Russell-Silver syndrome (RSS) is a heterogeneous disorder associated with pre- and post-natal growth restriction and relative macrocephaly. Involvement of imprinted genes on both chromosome 7 and 11p15.5 has been reported.

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.

Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome.

Background: The introduction of molecular karyotyping technologies facilitated the identification of specific genetic disorders associated with imbalances of certain genomic regions. A detailed phenotypic delineation of interstitial 16p13.3 duplications is hampered by the scarcity of such patients.

Molecular breakpoint mapping of 6q11-q14 interstitial deletions in seven patients.

Interstitial deletions involving 6q11-q14 have been reported in less than 20 patients, with the breakpoints studied by G-banding alone. We report on seven patients with 6q11-q14 interstitial deletions of variable size. The breakpoints were studied by G-banding, dual-color BAC-FISH and SNP array.

Submicroscopic deletions of 11q24-25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH.

Background: Jacobsen syndrome is a rare contiguous gene disorder that results from a terminal deletion of the long arm of chromosome 11. It is typically characterized by intellectual disability, a variety of physical anomalies and a distinctive facial appearance. The 11q deletion has traditionally been identified by routine chromosome analysis.

Craniosynostosis associated with distal 5q-trisomy: further evidence that extra copy of MSX2 gene leads to craniosynostosis.

Distal 5q-trisomy has been reported in less than 30 patients, with craniosynostosis present in five. We report two new patients with distal 5q-trisomy craniosynostosis. Patient 1 had mild Kleeblattschädel with synostosis of multiple sutures together with wide and medially deviated thumbs and halluces, indicative of Pfeiffer syndrome.

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.

Postnatal follow-up of prenatally diagnosed trisomy 16 mosaicism.

Objective: To determine the long-term outcome of pregnancies prenatally diagnosed with trisomy 16 and identify variables associated with the outcome.

Methods: We reviewed all published and our unpublished data from trisomy 16 pregnancies for which outcomes were available for children of greater than 1 year of age.

Results: Nineteen cases were diagnosed with trisomy 16 on chorionic villus sampling (CVS) and 17 cases at amniocentesis.

Identification and functional characterization of 2 variant alleles of the telomerase RNA template gene (TERC) in a patient with dyskeratosis congenita.

Heterozygous mutations of the human telomerase RNA template gene (TERC) have been described in patients with acquired aplastic anemia and the autosomal dominant form of dyskeratosis congenita (DKC). Patients with mutations in both TERC alleles have not yet been reported. Here, we report a patient with DKC who inherited 2 distinct TERC sequence variants from her parents; a deletion (216_229del) in one and a point mutation (37A>G) in the other allele of the TERC gene.

Beta-thalassemia in association with a new delta-chain hemoglobin variant [delta116(g18)Arg-->Leu]: implications for carrier screening and prenatal diagnosis.

We describe a complicated genetic counseling and prenatal diagnostic case involving an East Indian couple that had lost two consecutive pregnancies. Hemoglobinopathy screening was conducted to investigate the possibility of Hb Bart's hydrops fetalis or Hb H hydrops fetalis. The initial work-up indicated that alpha-thalassemia was not a contributing factor, with both parents being carriers of single gene deletions (-alpha(3.