Identification of aU2HRgene mutation in Turkish families with Marie Unna hereditary hypotrichosis

Abstract

Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of isolated alopecia. The disorder is characterized by the absence or scarcity of scalp hair, eyebrows and eyelashes at birth. Coarse wiry hair begins to grow during childhood, but this is followed by progressive hair loss, which usually begins around puberty. A recent study identified mutations in U2HR, an inhibitory upstream open reading frame in the 5'-untranslated region of the human hairless gene. We investigated three reportedly unrelated Turkish multigeneration families with MUHH. Using direct sequencing of U2HR we were able to identify the c. 2T>A (p.M1K) mutation in one index patient of each family. The mutation cosegregates perfectly with the disease in all members of the families. To our knowledge, this is the first time that a mutation in U2HR has been identified in families from the Middle East. The observation of a common mutation is suggestive of a possible founder effect.

A splice variant in KRT71 is associated with curly coat phenotype of Selkirk Rex cats

“…The autosomal dominant forms of woolly hair / hair loss disorders in human have been shown to result from mutations in corneodesmosin ( CDSN )22, the inhibitory upstream open reading frame (U2HR) of hairless ( HR )2324, APC-downregulated-by-1 ( APCDD1 )25, Kertain-71 26 and Keratin-74 14. Yet human studies have not fully elucidated the molecular basis of hereditary hair disorders; hence, a better determination of pathogenic dominant mutations within genes is necessary.…”

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

“…To date, 14 distinct mutations have been identified in 19 MUHH families of various ethnicities 17,18 and in one Chinese patient. 22 This mutation spectrum includes single-base substitutions clustered at the initiation or termination codons of U2HR, and two nonsense mutations.…”

“…1 Further German MUHH families [5][6][7][8][9] and a number of families of other ethnicities have been reported in recent years. [10][11][12][13][14][15][16][17][18] To identify the causal gene for MUHH, van Steensel et al 12 performed a genomewide linkage study in one Dutch and one British family and mapped the gene for MUHH to chromosome 8p21. This region is close to the human hairless (HR) gene, mutations of which, affecting the coding region or splice sites, are responsible for autosomal recessive congenital atrichia.…”

Nucleic acid‐based non‐invasive prenatal diagnosis of genetic skin diseases: are we ready?

“…In 2009, Wen et al discovered that the culprit gene behind the rare MUHH is U2HR, the second upstream open reading frame in the 5′UTR of HR gene (41). So far, all the reported mutations in U2HR are single nucleotide substitutions (41,(44)(45)(46)(47)(48)(49)(50).…”