Distinct phenotypic features and gender-specific disease manifestations in a Spanish family with desmin L370P mutation

Desminopathies represent a subtype of myofibrillar myopathy caused by mutations in the DES gene, which cause myofibril disruption and intracellular inclusions containing desmin and other protein components. Desminopathy mainly involves skeletal and cardiac muscle, separately or together. Both autosomal dominant and autosomal recessive inheritance have been reported. Here, we describe the second family identified to date with an L370P desmin mutation. The disease in this family shows autosomal dominant inheritance with a particular phenotype, where males suffer from sudden death of cardiac origin while females exhibit a more benign myopathy of distal onset and slower progression. Because the only family previously identified with this mutation was limited to one studied patient, the present kindred represents the largest clinical investigation of the phenotype associated with the L370P mutation.     

Increased levels of diadenosine polyphosphates in dry eye

PURPOSE: To analyze the levels of the diadenosine polyphosphates Ap4A and Ap5A in tears, in a set of control subjects and in groups of symptomatic and nonsymptomatic persons with dry eye. METHODS: Ninety-seven subjects participated in the study. The subjects were divided into five experimental groups: control subjects; symptomatic patients with normal tear secretion; symptomatic patients with low tear secretion; forced blink; and corneal mechanical stimulation provided by a gas esthesiometer. The Schirmer I test was used to measure and collect tear secretions from each subject. All samples were processed by high pressure liquid chromatography (HPLC) and their Ap4A and Ap5A levels determined. RESULTS: The levels of Ap4A and Ap5A in tears were greater in all symptomatic patients than in control subjects, especially in symptomatic subjects with low tear secretion. Within the symptomatic subjects with normal tear secretion, significant differences in concentrations of Ap4A and Ap5A were found between men and women. In the forced blink experiments, concentrations of the Ap4A and Ap5A rose with increasing blink frequency. When the cornea was mechanically stimulated, the levels of Ap4A and Ap5A rose significantly during both moderate and high-flow rate tests. CONCLUSIONS: The increased levels of Ap4A and Ap5A in tears of patients with dry eye allow these dinucleotides to be used as objective biomarkers in dry eye conditions.     

Genetic diversity of nine STRs in two northwest Iberian populations: Galicia and northern Portugal

The genotyping of two population samples from Galicia and northern Portugal was performed for nine STR loci using a single multiplex reaction with the AmpFlSTR Profiler Plus PCR amplification kit which co-amplifies the systems D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820 and the X-Y homologous gene amelogenin. Allele frequencies for these nine tetranucleotide repeat markers were calculated and no significant differences were observed when comparing these two populations. Conformity with Hardy-Weinberg equilibrium proportions was good for all systems in both samples. The combined power of exclusion was 99.981% and 99.980% in Galicia and northern Portugal, respectively and the combined power of discrimination was greater than 99.999%. Segregation analysis of all loci detected two incompatibilities, one in D3S1358 (out of 112 meioses) and another in D7S820 (out of 104 meioses). Both could be explained by single-step mutations. In general co-amplification was good except for some relatively degraded samples in which poor amplification was observed for the largest STRs. Nevertheless the system is technically robust even when small amounts of template DNA are used and in addition is highly informative and time-saving. However, caution should be taken in the interpretation of profiles in degraded samples and the apparently high mutation rate of D3S1358 and D7S820 should also be kept in mind. Received: 6 April 1999 / Accepted: 16 July 1999     

Behavior of loci D1S1656 and D12S391 in a sample from Maracaibo,Venezuela

Two recently reported short tandem repeat polymorphisms characterized by PCR, D1S1656 and D12S391, were investigated in a sample from Maracaibo, an admixed population of Venezuela, in order to evaluate their application in forensic and population genetics studies. The unbiased heterozygosities were 0.9011 and 0.8444 for locus D1S1656 and D12S391, respectively. The joint discrimination power and joint probability of exclusion were 0.99972 and 0.93287. When allele frequencies of locus D1S1656 from Maracaibo were compared with eight other populations, our group clustered with the European or European‐derived samples, mainly from Spain. In the comparison of locus D12S391 with 16 populations, Maracaibo clustered with 3 Asian samples. The high heterozygosity and discrimination power make these two loci important candidates to be considered for STR packages for forensic and population genetic purposes. Am. J. Hum. Biol. 15:68–71, 2003. © 2002 Wiley‐Liss, Inc.     

Linkage analysis in a large Spanish family with X-linked retinitis pigmentosa: phenotype—genotype correlation

X-linked retinitis pigmentosa (XLRP) accounts for 10–25% of RP families and causes the most severe form of the disease in terms of onset and progression. Although three different loci (RP3, RP2 and RP15) have been proposed on the short arm of the X-chromosome by linkage analysis, RP3 represents the disease locus in the majority of XLRP families.
The identification of female carriers of X-linked RP is important for genetic counselling. The presence of fundus and electroretinogram (ERG) abnormalities have been reported to be as high as 87 and 90%, respectively. However, in clinical practice it has not always been possible to know the carrier state of females at risk.
Thirty-five members of a Spanish family with X-linked RP were evaluated by linkage analysis using nine polymorphic markers (CYBB, DXS1110, M6, DXS6679, DXS1068, DXS1058, MAOA, MAOB and DXS6849) that map to the X-chromosome region Xp21.1 to Xp11.3, in an attempt to determine the carrier state of these females at risk. It was possible to establish that a RP3 mutation is, most likely, segregating in this family.     

Population genetics of three VNTR polymorphisms in two different Spanish populations

Summary Two different Spanish populations, one from Galicia (NW Spain) and the other from the rest of Spain, have been analyzed at three different hypervariable loci (YNH24, MS43a and MS31) using the EDNAP electrophoretic protocol andHinfI as restriction enzyme. Although the rest of Spain population is a clearly stratified population using classical blood groups, no evidence of stratification for these loci has been found and the differences to the Galician population were not significant, which suggests that a common Spanish population database could be possible. A semiparametric model is proposed for estimating frequencies, using the smoothed cross-validation of Hall et al. (1992) to calculate the size of the window utilized.