Keywordsfatty aldehyde dehydrogenase; ichthyosis; mutation; Sjögren-Larsson syndrome Sjögren-Larsson syndrome (SLS; OMIM 270200) is an autosomal recessive disorder characterized by the presence of pruritic ichthyosis, mental retardation, spastic diplegia or tetraplegia, retinal perimacular 'glistening white dots' and photophobia. 1 SLS is caused by mutations in the ALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH), a microsomal enzyme that catalyses the oxidation of medium-and long-chain aliphatic aldehydes. 2 More than 70 mutations have been identified in this disease.3 Most mutations are unique to each SLS family, but several common mutations have been reported among patients from Europe and the Middle East. In the first molecular genetic analysis of a cohort of patients with SLS from Brazil, we now report a common disease-causing ALDH3A2 mutation, delineate its associated phenotypic spectrum and describe a diagnostic screening test using restriction enzyme digestion. Case and methodsNine patients with SLS from three apparently unrelated Brazilian kindreds native to the south and southeastern part of the country were studied. Patients 1, 2 and 3 were previously reported 4 and were born to consanguineous parents; patients 4, 5 and 6 are sisters and patients 7 and 8 are their cousins. Patient 9 was also born to first cousins. Blood specimens, Total genomic DNA was extracted from blood using standard phenol-chloroform methods. ALDH3A2 exons and their flanking sequences were amplified by polymerase chain reaction (PCR) and sequenced. 2 To detect the c.1108-1G → C mutation more conveniently, exon 8 was digested with DdeI according to the manufacturer's instructions and restriction products separated by agarose gel electrophoresis. ALDH3A2 haplotypes were determined using four intragenic single nucleotide polymorphisms as described. 2 FALDH enzyme activity was measured in cultured skin fibroblasts. 5Results and discussion Biochemical and molecular characterizationAll patients had <10% of normal FALDH enzyme activity in cultured skin fibroblasts ( Table 1). Sequencing of the ALDH3A2 gene revealed a homozygous c.1108-1G → C mutation in intron 7 of all of the affected individuals. Their parents were heterozygous for the mutation, except for the parents of patient 9 who were not tested. The c.1108-1G → C mutation abolishes a DdeI restriction enzyme cut site in the wild-type gene. DdeI digestion of a 275-bp PCR product of exon 8 and its flanking intron 7 sequence yielded a 181-bp fragment from normal control subjects, but a 263-bp fragment from the patients with SLS (Fig. 1b). This constitutes a convenient screening test for the mutation. Haplotype analysis of the ALDH3A2 gene showed that patients from each family were homozygous for haplo-type 1 (see Rizzo et al.2).The c.1108-1G → C mutation alters the splice acceptor site at the junction of intron 7 and exon 8. Like many exons, exon 8 does not end between codons, but rather ends with part of a codon, which is completed when exon 8 is spliced to exon 9...

Lymphoedema and skin naevi are common in children with Turner syndrome (TS). Lymphoedema in the early stages of fetal life is thought to cause several of the phenotypic characteristics in patients with TS such as nuchal folds and pterygium colli. We present two patients with TS who have unusual lesions on the scalp. The first patient had an oval circumscribed lesion. Two biopsies were obtained from the lesion. Increased numbers of collagen fibres were seen in the reticular dermis suggesting the diagnosis of connective tissue naevus. The second patient presented with an area with skin folds on the scalp, similar to cutis verticis gyrata. Although unusual in TS, both lesions could be considered as resolving stages of lymphoedema. We suggest that karyotyping should be performed in cases of female infants presenting with similar lesions.