Pitfalls of mapping a large Turkish consanguineous family with vertical monilethrix inheritance.
2009
Summary: Pitfalls of mapping a large Turkish consanguineous family with vertical monilethrix inheritance: Monilethrix, a rare autosomal dominant disease characterized by hair fragility and follicular hyperkeratosis, is caused by mutations in three type II hair cortex keratins. The human keratin family comprises 54 members, 28 type I and 26 type II. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. In our study, Monilethrix was diagnosed on the basis of clinical characteristics and microscopic examination in a family with 11 affected members. Haplotype analysis was performed by three Simple Tandem Repeat markers (STR) and KRT86 gene was sequenced for the identification of the disease causing mutation. In the results of this, autosomal dominant mutation (E402K) in exon 7 of KRT86 gene was identified as a cause of Moniltherix in the large family from Turkey. Key-words: Monilethrix - hHb6 coding keratin gene (KRT86) - Hotspot mutations - Haplotype - Single nucleotide polymorphism (SNP) - Dominant inheritance. INTRODUCTION Over the past decade, many molecular genetic studies established to link between the genes coding for keratin intermediate filament proteins and inherited skin and hair disorders. In 1997, it was demonstrated that the pathogenicity of mutated epithelial keratins holds also true for mutated hair keratins. The respective disease Monilethrix (OMIM # 158000), first described, in 1879 as a new disease entity (14) is reported as an autosomal dominant condition with high penetrance but variable expression and belongs to be variety of congenital hair diseases whose hallmark is an unusually deformed hair shaft (5, 12, 13,) (www.interfil.org). Keratin protein family consists of epithelial keratins expressed mainly in the epithelial tissues and hair keratins forming highly keratinized structures such as hairs, nails, etc. We now know that the human genome contains a total of 54 functional keratin genes which can be divided into 28 type I and 26 type II genes, forming two clusters of 27 genes each on chromosome 17q21.2and 12ql3. 13(10, 11). The type II basic keratins can be further divided into two groups. Group A contains structurally related Hbl (K81), Hb3 (K83), and Hb6 (K86), encoded by KRT81, KRT83 and KRT86 respectively, which are expressed in the hair cortex while group C contains Hb2 (K82), Hb4 (K84), and Hb5 (K85) expressed in the cuticle (2-4, 6, 13, 15). All disease-causing mutations described so far are found in genes encoding group A members of the type II hair keratins. Among them, KRT86 is the leading cause with hot spot mutations in exon 7. We present the analyses of a Turkish family with Monilethrix and discuss the pitfalls of haplotype mapping for KRT86 gene region, challenged by homozygous markers. The presented family is unique by being a large Monilethrix family with E402K mutation of K86, and the first report in the Black sea region of Turkey. Our result underlines that mapping of autosomal dominant disorder in closed populations or in large consanguineous families can be challenged homozygous haplotypes. CLINICAL EVALUATION The proband was a 2-year-old female child with very brittle, short and thin hair sparsely covering her entire scalp. Her eyebrows, eyelashes and nails were normal. Pedigree analysis revealed 10 other affected individuals, including her father and brother. The affected individuals were dispersed vertically over three generations (Fig. 1). Interviewing the family members revealed that some of the affected individuals were born without hair and remained with total alopecia, while others were born with normal hair, as was in our proband, but altered to sparse, dry, and brittle hair shortly after 2-3 months. All of the affected individuals were appointed for dermatological evaluation and hair samples were viewed under microscope. Affected members of the family displayed the typical phenotype of beaded and broken hairs. …
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
3
Citations
NaN
KQI