De Novo Inverted Duplication Deletion of 4p in a 14-Week-Old Male Fetus Aborted Due to Multiple Anomalies.

Inverted duplications deletions are rare, complex, and nonrecurrent chromosomal rearrangements associated with a variable phenotype. In this case report, we described the phenotype and genotype of a 14-week-old male fetus, who was aborted after discovery of multiple anomalies (septal cystic hygroma, open abdominal wall, and a nonidentifiable lower limb). At autopsy, fluorescence in situ hybridization and array comparative genomic hybridization identified an inverted duplication with terminal deletion of 4p [46,XY,der(4)del(p16.3)dup(4)(p15.2p16.3)]. Only five genotypically similar cases have been reported, and we hope our case contribution will add meaningful to the body of knowledge.

A ZFHX4 mutation associated with a recognizable neuropsychological and facial phenotype.

Several patients with chromosomal deletions including ZFHX4 gene have been described, whereas point mutations are very rare. This gene encodes for a transcription factor involved in the development of several embryonal processes, including brain differentiation. Patients with 8q21.11 deletions usually show intellectual disability, short stature, peculiar facial features, and severe eye abnormalities. We describe a female patient with mild intellectual disability, autism spectrum disorder, strabismus, ptosis, low-set and prominent ears, high-arched palate, microretrognathia. Clinical Exome Sequencing revealed the presence of a de novo heterozygous variant in ZFHX4. Therefore, we further investigate the different phenotypes of ZFHX4 mutations and 8q21.11 deletions.

Clinical, cytogenetic and molecular-cytogenetic characterization of a patient with a de novo tandem proximal-intermediate duplication of 16q and review of the literature.

Partial trisomy 16 is rare and most of the reported cases are secondary to chromosome rearrangements resulting in concurrent monosomies or trisomies of a second chromosome. Only a few patients survive the neonatal period and the duplication of the long arm seems to be mainly responsible for the prenatal lethality of the full trisomy 16. The reported patients with a partial 16q trisomy have a wide spectrum of congenital anomalies that include dysmorphic features, central nervous system malformations, failure to thrive, and club feet. The patients with duplications of proximal 16q frequently have short stature, developmental delay, speech delay, learning difficulties, and mild to severe behavioral problems. Here we describe a patient with an inverted de novo tandem duplication of 16q with breakpoints evaluated in detail by molecular-cytogenetic techniques. Main clinical features include postural, motor and speech delay with severe learning difficulties and behavioral problems, obesity, microcephaly, and mild dysmorphic features. In the report we attempt to classify the few reported patients with pure partial duplications of 16q in more narrow and homogeneous groups: proximal, proximal-intermediate, intermediate, and intermediate-distal duplications. Moreover, we emphasize the importance of proper cytogenetic investigation and complete molecular cytogenetic refinement in all cases with a suspected chromosomal anomaly.

Phenotypes of a naturally defective recB allele in Neisseria meningitidis clinical isolates.

Neisseria meningitidis strains belonging to the hypervirulent lineage ET-37 and several unrelated strains are extremely UV sensitive. The phenotype is consequent to the presence of a nonfunctional recB(ET-37) allele carrying multiple missense mutations. Phenotypic analysis has been performed with congenic meningococcal strains harboring either the wild-type recB allele or the recB(ET-37) allele. Congenic recB(ET-37) meningococci, in addition to being sensitive to UV, were defective both in repair of DNA lesions induced by UV treatment and, partially, in recombination-mediated transformation. Consistently, the wild-type, but not the recB(ET-37), allele was able to complement the Escherichia coli recB21 mutation to UV resistance and proficiency in recombination. recB(ET-37) meningococci did not exhibit higher frequencies of spontaneous mutation to rifampin resistance than recB-proficient strains. However, mutation rates were enhanced following UV treatment, a phenomenon not observed in the recB-proficient counterpart. Interestingly, the results of PCR-based assays demonstrated that the presence of the recB(ET-37) allele considerably increased the frequency of recombination at the pilin loci. The main conclusion that can be drawn is that the presence of the defective recB(ET-37) allele in N. meningitidis isolates causes an increase in genetic diversity, due to an ineffective RecBCD-dependent DNA repair and recombination pathway, and an increase in pilin antigenic variation.

Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein.

Rab4 and Rab11 are small GTPases belonging to the Ras superfamily. They both function as regulators along the receptor recycling pathway. We have identified a novel 80-kDa protein that interacts specifically with the GTP-bound conformation of Rab4, and subsequent work has shown that it also interacts strongly with Rab11. We name this protein Rab coupling protein (RCP). RCP is predominantly membrane-bound and is expressed in all cell lines and tissues tested. It colocalizes with early endosomal markers including Rab4 and Rab11 as well as with the transferrin receptor. Overexpression of the carboxyl-terminal region of RCP, which contains the Rab4- and Rab11-interacting domain, results in a dramatic tubulation of the transferrin compartment. Furthermore, expression of this mutant causes a significant reduction in endosomal recycling without affecting ligand uptake or degradation in quantitative assays. RCP is a homologue of Rip11 and therefore belongs to the recently described Rab11-FIP family.