Cockayne syndrome is an autosomal recessive multisystem disorder characterized principally by neurological and sensory impairment, cachectic dwarfism, and photosensitivity. This rare disease is linked to mutations in the CSB/ERCC6 and CSA/ERCC8 genes encoding proteins involved in the transcription-coupled DNA repair pathway. The clinical spectrum of Cockayne syndrome encompasses a wide range of severity from severe prenatal forms to mild and late-onset presentations. We have reviewed the 45 published mutations in CSA and CSB to date and we report 43 new mutations in these genes together with the corresponding clinical data. Among the 84 reported kindreds, 52 (62%) have mutations in the CSB gene. Many types of mutations are scattered along the whole coding sequence of both genes, but clusters of missense mutations can be recognized and highlight the role of particular motifs in the proteins. Genotype-phenotype correlation hypotheses are considered with regard to these new molecular and clinical data. Additional cases of molecular prenatal diagnosis are reported and the strategy for prenatal testing is discussed. Two web-based locus-specific databases have been created to list all identified variants and to allow the inclusion of future reports (www.umd.be/ CSA/ and www.umd.be/CSB/). Hum Mutat 31:113-126,

A dozen years have passed since the first genetic lesion was identified in a family with craniosynostosis, the premature fusion of the cranial sutures. Subsequently, mutations in the FGFR2, FGFR3, TWIST1, and EFNB1 genes have been shown to account for approximately 25% of craniosynostosis, whilst several additional genes make minor contributions. Using specific examples, we show how these discoveries have enabled refinement of information on diagnosis, recurrence risk, prognosis for mental development, and surgical planning. However, phenotypic variability can present a significant challenge to the clinical interpretation of molecular genetic tests. In particular, the difficulty of analyzing the complex interaction of genetic background and prenatal environment in determining clinical features, limits the value of identifying low penetrance mutations.

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High oleic acid to linoleic acid ratios (high O/L) in tetraploid peanut (Arachis hypogaea L.) are controlled by the activity of oleoyl‐PC desaturase, which is encoded by two homeologous genes (ahFAD2A and ahFAD2B). In a naturally occurring high O/L peanut, a spontaneous mutation (G‐to‐A at position 448 resulting in a D150N amino acid substitution) has been found in ahFAD2A, which resulted in a dysfunctional desaturase. In normal × high O/L crosses, segregation ratios for high:normal O/L are either 1:3 or 1:15 suggesting that one gene in some normal O/L lines may be mutated. We designed a cleaved amplified polymorphic sequence (CAPS) marker to differentiate the mutant and wild‐type ahFAD2A alleles at the critical point mutation. The mutant allele was present in 31.6% of the accessions from the mini‐core collection of peanut germplasm and was confirmed by DNA sequence analysis. The mutant allele was frequent among subspecies hypogaea accessions but absent from subspecies fastigiata accessions and the putative diploid, A‐genome progenitor of peanut, Arachis duranensis These data will be useful to breeders who would like to transfer disease resistance traits from mini‐core accessions to high oleic acid cultivars.

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Nucleotide excision repair associated diseases comprise overlapping phenotypes and a wide range of outcomes. The early stages still remain under‐investigated and underdiagnosed, even although an early recognition of the first symptoms is of utmost importance for appropriate care and genetic counseling. We systematically collected clinical and molecular data from the literature and from newly diagnosed NER patients with neurological impairment, presenting clinical symptoms before the age of 12 months, including foetal cases. One hundred and eighty‐five patients were included, 13 with specific symptoms during foetal life. Arthrogryposis, microcephaly, cataracts, and skin anomalies are the most frequently reported signs in early subtypes. Non ERCC6/CSB or ERCC8/CSA genes are overrepresented compared to later onset cohorts: 19% patients of this cohort presented variants in ERCC1, ERCC2/XPD, ERCC3/XPB or ERCC5/XPG. ERCC5/XPG is even the most frequently involved gene in foetal cases (10/13 cases, [4/7 families]). In this cohort, the mutated gene, the age of onset, the type of disease, severe global developmental delay, IUGR and skin anomalies were associated with earlier death. This large survey focuses on specific symptoms that should attract the attention of clinicians towards early‐onset NER diagnosis in foetal and neonatal period, without waiting for the completeness of classical criteria.

A dozen years have passed since the first genetic lesion was identified in a family with craniosynostosis, the premature fusion of the cranial sutures. Subsequently, mutations in the FGFR2, FGFR3, TWIST1, and EFNB1 genes have been shown to account for approximately 25% of craniosynostosis, whilst several additional genes make minor contributions. Using specific examples, we show how these discoveries have enabled refinement of information on diagnosis, recurrence risk, prognosis for mental development, and surgical planning. However, phenotypic variability can present a significant challenge to the clinical interpretation of molecular genetic tests. In particular, the difficulty of analyzing the complex interaction of genetic background and prenatal environment in determining clinical features, limits the value of identifying low penetrance mutations.