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We have identified nonsense mutations in the gene CDSN (encoding corneodesmosin) in three families suffering from hypotrichosis simplex of the scalp (HSS; OMIM 146520). CDSN, a glycoprotein expressed in the epidermis and inner root sheath (IRS) of hair follicles, is a keratinocyte adhesion molecule. Truncated CDSN aggregates were detected in the superficial dermis and at the periphery of hair follicles. Our findings suggest that CDSN is important in normal scalp hair physiology.

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Hereditary angioedema (HAE) is becoming much more genetically complex than was initially considered. Thus, the role of HAE genetics is expanding beyond research laboratories and the genotyping of subjects suffering from HAE has become diagnostically indispensable in clinical practice. The synthesis and interpretation of the clinical and biochemical analyses to facilitate appropriate genetic test selection has thus also become significantly more complex. With this in mind, an international multidisciplinary group of 13 experts in HAE genetics and disease management was convened in October 2018. The objective was to develop clear, actionable, evidence-and consensus-based statements aiming to facilitate the communication between physicians treating HAE patients and clinical geneticists, and thus promote the effective use of genetics in the management of the disease. Eleven consensus statements were generated, encompassing considerations regarding the clinical indications for genotyping angioedema patients, the methods of detection of HAE causative variants, the variant pathogenicity curation, the genotyping of HAE patients in the clinic, and genetic counseling. These statements are intended both to guide clinicians and to serve as a framework for future educational and further genetic testing developments as the field continues to evolve rapidly.

Recurrent angio-oedema is a sign of various acquired and inherited disease entities, including hereditary angio-oedema types I and II that result from a genetic deficiency of C1 inhibitor, and a recently described type of dominantly inherited angio-oedema, which does not show a deficiency of C1 inhibitor. Until now, this new type of hereditary angio-oedema, designated as hereditary angio-oedema type III, has been assumed to be a disorder specific to females. We now describe a four-generation family with dominantly inherited angio-oedema and normal C1 inhibitor in which, in contrast to all previous observations, not only five female but also three male family members were clinically affected. One male patient was mainly affected following the intake of angiotensin-converting enzyme inhibitors. Our current observation leads to new considerations about the classification of hereditary angio-oedema with normal C1 inhibitor. Either hereditary angio-oedema with normal C1 inhibitor can be an entity affecting females predominantly, but not exclusively; in that case, men appear to have a much reduced chance of clinical manifestations. Alternatively, our present observation of hereditary angio-oedema with normal C1 inhibitor affecting both sexes may represent a new disease entity, presumably with a different underlying defect.

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HLA antigens were determined in two infants with multiple congenital anomalies and in their healthy parents and one sibling. One infant had a deletion of a major portion of the long arm of chromosome 6. The other child had a translocation of a similar piece of chromosome 6 to the short arm of chromosome 3. The mother and the maternal grandmother showed this translocation in a balanced state. The HLA types of both children and their parents exclude the localization of the major histocompatibility locus from the deleted or translocated portion of the long arm of chromosome 6.