Mutations of GJB2 (encoding connexin 26) are the most common cause of hearing loss (HL) in different populations, and a broad spectrum of GJB2 mutations has been identified. We screened 204 consecutive patients with non-syndromic sensorineural hearing loss for GJB2 mutations. Causative GJB2mutations were identified in 31 (15.2%) patients, and two common mutations, c.35delG and L90P (c.269T>C), accounted for 72.1% and 9.8% of GJB2 disease alleles. In four additional patients (2.0%) only one recessive GJB2 mutation was identified, making genetic counselling difficult. No genotype-phenotype correlation was established. We found, however, that homozygotes for truncating mutations were more likely to have a more severe degree of HL compared with other genotypes. Moreover, we showed by co-segregation studies that L90P is a GJB2 disease allele, and that compound heterozygotes for L90P and any recessive mutation share a mild to moderate phenotype. GJB2-associated HL was linked with progressive HL or with recurrent sudden sensorineural hearing loss (SSNHL) in three of 15 cases being analysed retrospectively. We extended the phenotypic spectrum of GJB2-related disease and recommend GJB2 mutation screening also in cases of progressive HL, and recurrent SSNHL. In addition, a carrier frequency of 1/110 (0.9%) for the most common Caucasian mutation in this gene, c.35delG, was determined in 1,212 blood donors from West-Austria, supporting the prevailing hypothesis of a Mediterranean founder mutation. Based on population and patient data, an overall GJB2 mutation carrier frequency of 1.3% was estimated for West-Austria.

We report a dysmorphic boy with a de novo partial trisomy lq. The boy has microcephaly, bilateral cleft lip and palate, low set and dysmorphic ears, brain anomalies, pulmonary stenosis, duodenal obstruction, dysplastic kidneys, and bifid thumbs. The trisomic segment lq32-qter is duplicated with an inverted insertion at lp36.3. The aberration was initially detected at amniocentesis and confirmed and defined by GTG banding, chromosome microdissection, and FISH on postnatal blood samples. The parents had normal karyotypes. De novo partial duplications of chromosome lq have rarely been reported. Comparison of our patient with other published pure trisomy lq cases showed similarities which allowed the further delineation of the trisomy lq syndrome.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder that results from an expanded trinucleotide (CAG) repeat on the huntingtin gene. Neurodegeneration in HD affects most prominently the basal ganglia. Therefore, diffusivity was obtained in the basal ganglia and thalamus of 29 patients with early HD and 27 healthy volunteers by means of the trace of the diffusion tensor (Trace(D)). Putaminal, caudate, pallidal, and thalamic Trace(D) values were increased in patients with HD compared with controls. Increased diffusivity in the putamen and caudate nucleus correlated with global functional impairment, CAG repeat length, as well as bicaudate ratio. Diffusion-weighted imaging appears to be a promising surrogate marker for disease severity in HD. Sensitivity to change remains to be established longitudinally.