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Editor—In 1994, we reported a 13 year old patient with 18p deletion and ulerythema ophryogenes and keratosis pilaris.1 We then suggested that this observation may be helpful in future attempts to localise the gene defect responsible for follicular genokeratoses, even though similar skin lesions have been reported in a number of patients with various chromosomal disorders, including sex chromosome aneuploidies. Remarkably, in addition to the report by Horsley et al,2 two further observations of this association were recently reported.3 4 This confirmed the presence of a true association and prompted a further look into the material that we obtained from the biopsy of our patient,1 searching for possible genes localised in the deletion area that may have a role in the pathogenesis of keratosis pilaris or ulerythema ophryogenes.
Indeed, the human laminin α1 chain is encoded by an approximately 9.5 kb mRNA transcribed from the LAMA1 gene, which is located on human chromosome 18p11.3,5 6 an area included in our patient's deletion. Laminin α1 chain is one of the three chains of laminin 1 (α1β1γ1) and laminin 3 (α1β2γ1).7 Laminin 1 is present in a pattern encircling the embryonic spinal cord and is ubiquitously expressed in epithelium and endothelium, whereas laminin 3 is found at the ventromedial surface of the developing cord and is expressed in neural synapses.8 Broad immunolabelling of the laminin α1 chain has also been detected in the basement membrane of the serous and mucous acini and of the intercalated, striated, and excretory ducts of the human salivary gland.9 In addition, laminin 1 was found involved in acinar formation of a human submandibular gland cell line.10
We used an antibody that identifies the human laminin α1 chain, as previously described,9 and stained our patient's tissue.1 Indeed, laminin α1 chain was totally absent from vessels, adnexal structures, and dermal nerves in the patient's skin (fig 1). In addition, sebaceous glands were not present in the involved skin areas.
It is unclear whether the lack of expression ofLAMA1 in our patient has a causal association with his cutaneous clinical findings or it is an epiphenomenon. Other patients with keratosis pilaris or ulerythema ophryogenes have not been studied for LAMA1expression, and such biopsies were not available to us for the present study (the control presented in fig 1 is from a patient with normal skin findings). Our patient is presumably haploinsufficient forLAMA1; thus, some level of expression of that gene should have been seen. Haploinsufficiency forLAMA1 could not have caused the genodermatosis of our patient, unless the formation of the trimeric laminin 1 is disturbed in the presence of deficient synthesis of the α1 chain. It is also possible that the deletion unmasked a recessive mutation by the loss of the wild type allele in the deleted part of chromosome 18, as suggested by Nazarenko et al 4 for other genes in the area. Another possibility is that of imprinting of the normalLAMA1 allele; the gene is indeed located in an area of chromosome 18 that has been associated with non-Mendelian features in inherited bipolar disorder.11 Although it is difficult to implicate directly LAMA1 in the pathogenesis of keratosis pilaris/ulerythema ophryogenes, the findings in our patient should prompt further investigation of the direct or indirect role of LAMA1 in these diseases.
We conclude that observations made by us1 and Horsley et al 2 were recently confirmed by others.3 4 There seems to be an association between keratosis pilaris/ulerythema ophryogenes and partial monosomy of chromosome 18. This association indicates the presence of gene(s) in the 18p area that regulate follicular keratinisation and formation of sebaceous gland structures. Laminin α1 deficiency may offer a direct or indirect explanation for these abnormalities; however, other gene(s) in the area should be investigated, too.
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