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Acromelic frontonasal dysostosis ( AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 36 ( SCA36) is a new SCA subtype recently reported in Japanese and Spanish pedigrees. To assess the frequency and clinical characteristics of SCA36 in patients from Mainland China, we combined the repeat-primed polymerase chain reaction method and Southern blot analysis to detect the GGCCTG hexanucleotide repeats of NOP56 in 364 probands with SCA, 126 probands with hereditary spastic paraplegia and 99 probands with amyotrophic lateral sclerosis ( ALS). Systematic and targeted clinical evaluations and investigations were conducted in the SCA36 patients. As a result, eight autosomal dominant spinocerebellar ataxia ( ADCA) pedigrees (a total of 13 patients) and one sporadic SCA (S- SCA) patient were identified as SCA36 in the SCA cohort, accounting for approximately 1.60% of the cases in the ADCA group and 0.32% of those in the S- SCA group in Mainland China. The characteristics include late onset and slow progression accompanied by acoustic impairments and 'possible' ALS phenotype in patients from Mainland China. [ABSTRACT FROM AUTHOR]

Xiong F, Sun M, Zhang X, Cai R, Zhou Y, Lou J, Zeng L, Sun Q, Xiao Q, Shang X, Wei X, Zhang T, Chen P, Xu X. Molecular epidemiological survey of haemoglobinopathies in the Guangxi Zhuang Autonomous Region of southern China. Accurate and up-to-date data on the frequency of haemoglobinopathies among the populations of Guangxi Zhuang Autonomous Region, where haemoglobinopathies are most endemic in China, are required. In our study, a total of 5789 samples obtained from members of the Han, Zhang, and Yao ethnic groups in six geographical areas of Guangxi Province were analysed systematically in terms of both haematological and molecular parameters. The results presented that the total heterozygote frequency of thalassaemias and other haemoglobinopathies was 24.51%, of which 17.55% was due to α-thalassaemia, 6.43% to β-thalassaemia, 0.38% to structural haemoglobin variants, and 0.16% to δ-thalassaemia. The mutational spectrum among the local population for each type of disorder was described, including the first report on the true prevalence of three silent α thalassemia defects, −α3.7/(4.78%), −α4.2/(1.61%) and Hb Westmead (αWSα/) (1.57%) and of δ-thalassemia resulting from five novel and two rare mutations never before identified in Chinese individuals. Comparison of the frequencies of α-globin mutations among the ethnic groups showed that there was a statistically significant difference between the Han (15.71%) and Zhuang (20.12%), and between the Han (15.71%) and Yao (20.84%) ethnic groups. In addition, we have performed the first extensive study of haematological parameters of the Hb Westmead mutation using a group of Chinese subjects with compound heterozygosity for this variant and an α-thalassaemia deletion. The knowledge gained in this study will enable us to estimate the health burden in this high-risk population and to elucidate the various genetic alterations that underlie haemoglobinopathies. [ABSTRACT FROM AUTHOR]