Marie Unna hereditary hypotrichosis: Identification of a U2HR mutation in the family from the original 1925 report

Silke Redler, MD
- Institute of Human Genetics, University of Bonn, Bonn, Germany
- Reprint requests: Silke Redler, MD, Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany.
Roland Kruse, MD
- Dermatological Practice, Paderborn, Germany
Sibylle Eigelshoven, MD
- Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany
Sandra Hanneken, MD
- Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany
Melanie Refke
- Institute of Human Genetics, University of Bonn, Bonn, Germany
Yaran Wen, MD
- McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Xue Zhang, MD, PhD
- McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Sven Cichon, PhD
- Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
Regina C. Betz, MD
- Institute of Human Genetics, University of Bonn, Bonn, Germany
Markus M. Nöthen, MD
- Institute of Human Genetics, University of Bonn, Bonn, Germany
- Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

Accepted 9 June 2010. published online 26 July 2010.
Corrected Proof

Background

In 1925, Dr Marie Unna described a rare form of hereditary hypotrichosis in a German multigenerational family. This was later termed “Marie Unna hereditary hypotrichosis” (MUHH). MUHH is an autosomal dominant disorder that is characterized by the absence or scarcity of scalp hair, eyebrows, and eyelashes at birth; coarse and wiry hair during childhood; and progressive hair loss beginning around puberty. Causal mutations in U2HR, an inhibitory upstream open reading frame in the 5'-untranslated region of the human hairless (HR) gene, were recently identified in several unrelated MUHH families from various ethnic backgrounds.

Objective

Although there have been several clinical reports of descendants of the originally described family, the molecular cause of disease in this particular family has not been established. The aim of this study was to investigate descendants of this family and to analyze their DNA for the presence of U2HR mutations.

Methods

Descendants of the family (including one affected individual) were examined clinically. Direct sequencing of U2HR was performed. Enzymatic digestion using the restriction enzyme NcoI was performed to confirm the sequencing results.

Results

The index patient displayed the typical MUHH pattern of hair loss and was found to carry the disease-causing c.3G>A (p.M1I) U2HR mutation. This mutation was not detected in unaffected family members.

Limitations

Only one affected family member was investigated.

Conclusions

Eighty-five years after the first description of this rare form of alopecia, the disease-causing mutation in the originally reported family has been identified.

Key words: alopecia, hair loss, hypotrichosis, loss of function mutation, U2HR

Dr Redler is a recipient of a BONFOR fellowship from the medical faculty of the University of Bonn. Dr Nöthen is an Alfried Krupp von Bohlen und Halbach Professor of Genetic Medicine. Dr Betz is a recipient of an Emmy-Noether fellowship.

Conflicts of interest: None declared.

PII: S0190-9622(10)00693-6

doi:10.1016/j.jaad.2010.06.013

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