An intronic splice site alteration in combination with a large deletion affecting VPS13B (COH1) causes Cohen syndrome.

Cohen syndrome (CS) is a rare, autosomal recessive disorder characterized by intellectual disability, postnatal microcephaly, facial abnormalities, abnormal truncal fat distribution, myopia, and pigmentary retinopathy. It is often considered an underdiagnosed condition, especially in children with developmental delay and intellectual disability. Here we report on four individuals from a large Jordanian family clinically diagnosed with CS.

Presence of harmless small supernumerary marker chromosomes hampers molecular genetic diagnosis: a case report.

Mental retardation is correlated in approximately 0.4% of cases with the presence of a small supernumerary marker chromosome (sSMC). However, here we report a case of a carrier of a heterochromatic harmless sSMC with fragile X syndrome (Fra X).

The human genome puzzle - the role of copy number variation in somatic mosaicism.

The discovery of copy number variations (CNV) in the human genome opened new perspectives in the study of the genetic causes of inherited disorders and the etiology of common diseases. Differently patterned instances of somatic mosaicism in CNV regions have been shown to be present in monozygotic twins and throughout different tissues within an individual. A single-cell-level investigation of CNV in different human cell types led us to uncover mitotically derived genomic mosaicism, which is stable in different cell types of one individual.

Marfan syndrome with neonatal progeroid syndrome-like lipodystrophy associated with a novel frameshift mutation at the 3' terminus of the FBN1-gene.

We report on a 25-year-old woman with pronounced generalized lipodystrophy and a progeroid aspect since birth, who also had Marfan syndrome (MFS; fulfilling the Ghent criteria) with mild skeletal features, dilated aortic bulb, dural ectasia, bilateral subluxation of the lens, and severe myopia in addition to the severe generalized lipodystrophy. She lacked insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes. Mutation analysis in the gene encoding fibrillin 1 (FBN1) revealed a novel de novo heterozygous deletion, c.

Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome.

Neurofibromatosis-Noonan syndrome (NFNS), an entity which combines both features of Noonan syndrome (NS) and neurofibromatosis type 1 (NF1), was etiologically unresolved until recent reports demonstrated NF1 mutations in the majority of patients with NFNS. The phenotypic overlap was explained by the involvement of the Ras pathway in both disorders, and, accordingly, clustering of the NF1 mutations in the GTPase-activating protein (GAP) domain of neurofibromin was observed in individuals with NFNS. We report on an 18-month-old girl with typical findings suggestive of NS in combination with multiple café-au-lait spots and bilateral optic gliomas suggestive of NF1.