Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy.

Duplications in Xq28 involving MECP2 have been described in patients with severe mental retardation, infantile hypotonia, progressive spasticity, and recurrent infections. However, it is not yet clear to what extent these and accompanying symptoms may vary. In addition, the frequency of Xq28 duplications including MECP2 has yet to be determined in patients with unexplained X-linked mental retardation and (fe)males with severe encephalopathy.

Unique occurrence of Brachmann-de Lange syndrome in a fetus whose mother presented with a diffuse large B-cell lymphoma.

Brachmann-De Lange Syndrome (BDLS, MIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by a variable phenotype including intrauterine fetal growth retardation, limb reduction and distinctive facial and skull features (low frontal hairline, synophrys, anteverted nostrils, long philtrum, downturned corners of the mouth, micro- and retrognathia, low-set ears and micro-/brachycephaly), as well as a significant psychological developmental delay. A proposed classification system for BDLS include a classic type with characteristic facial and skull changes, a mild type where similar changes may develop with time or may be partially expressed, and a third type including phenocopies, where phenotypic changes are casually related to chromosomal aneuploidies or teratogenic exposures. We report on a 22-week gestation fetus with BDLS, showing intrauterine fetal growth retardation, brachycephaly, micro-/retrognathia and monolateral single bone of the forearm, in a woman harboring diffuse large B-cell lymphoma.

Trisomy 8q and partial trisomy 22 in a 43-year-old man with moderate intellectual disability, epilepsy and large cell non-Hodgkin lymphoma.

Partial trisomies are chromosome abnormalities resulting in a broad range of malformations depending on the size and location of the chromosomal rearrangement. Whereas diagnosis of these syndromes is usually made in early childhood, few descriptions exist about the clinical picture in adulthood. We report on a patient diagnosed at the age of 43 years with a 47,XY,+der(22)t(8;22)(q24.

Survival up to age 10 years in a patient with partial duplication 6q: case report and review of the literature.

Partial duplication of chromosome 6q has been recognized as a distinct dysmorphic syndrome with severe psychomotor and growth retardation, typical craniofacial features including microcephaly and microstomia, neck webbing, congenital contractures, and variable internal malformations. Most patients have died in the first year of life. We describe the clinical features and disease course in a boy with a duplication of 6q23.

Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation.

In families with nonsyndromic X-linked mental retardation (NS-XLMR), >30% of mutations seem to cluster on proximal Xp and in the pericentric region. In a systematic screen of brain-expressed genes from this region in 210 families with XLMR, we identified seven different mutations in JARID1C, including one frameshift mutation and two nonsense mutations that introduce premature stop codons, as well as four missense mutations that alter evolutionarily conserved amino acids. In two of these families, expression studies revealed the almost complete absence of the mutated JARID1C transcript, suggesting that the phenotype in these families results from functional loss of the JARID1C protein.