Mutations in the<i>P2RY5</i>gene underlie autosomal recessive hypotrichosis in 13 Pakistani families

Tariq, Muhammad; Ayub, Muhammad; Jelani, Musharraf; Basit, Sulman; Naz, Gul; Wasif, Naveed; Raza, Syed M.; Naveed, Abdul Khaliq; Khan, Saadullah; Azeem, Zahid; Yasinzai, Masoom; Wali, Abdul; Ali, Ghazanfar; Chishti, Muhammad Salman; Ahmad, Wasim

doi:10.1111/j.1365-2133.2009.09046.x

Cited by 19 publications

(23 citation statements)

References 16 publications

(56 reference statements)

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“…The autosomal recessive forms of hair loss disorders have been shown to result from mutations in hairless (HR, MIM 225060) Cichon et al 1998), desmoglein 4 (DSG4, MIM 607892) (Kljuic et al 2003), lipase-H (LIPH, MIM 607365) (Kazantseva et al 2006;Ali et al 2007), G-protein coupled receptor (P2RY5, MIM 609239) (Shimomura et al 2008;Pasternack et al 2008;Azeem et al 2008;Tariq et al 2009) and desmocollin-3 (DSC3, MIM 600271) ) genes. The genes for the three recently reported autosomal recessive forms of hair loss disorders (Naz et al 2010;Basit et al 2010a, b) have not been identified to date.…”

Section: Introductionmentioning

confidence: 99%

Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families

et al. 2010

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Autosomal dominant woolly hair (ADWH) is an inherited condition of tightly curled and twisted scalp hair. Recently, a mutation in human keratin-74 (KRT74) gene has been shown to cause this form of hereditary hair disorder. In the present study, we have described two families (A and B) having multiple individuals affected with autosomal dominant form of hair loss disorders. In family A, 10 individuals showed ADWH phenotype while in the family B, 14 individuals showed hypotrichosis of the scalp. Genotyping using polymorphic microsatellite markers showed linkage of both the families to type II keratin gene cluster on the chromosome 12q12-14.1. Mutation analysis of the KRT74 gene identified two novel mutations in the affected individuals of the families. The sequence analysis revealed a splice acceptor site mutation (c.IVS8-1G>A) in family A and a missense variant (c.1444G>A, p.Asp482Asn) in family B. Mutations identified in the present study extend the body of evidence implicating the KRT74 gene in the pathogenesis of autosomal dominant hair loss disorders.

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Section: Introductionmentioning

confidence: 99%

Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families

et al. 2010

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“…Previously, several mutations in the P2RY5 gene encoding G-protein-coupled receptor (P2Y5) has been reported to cause autosomal recessive hypotrichosis (Pasternack et al 2008;Azeem et al 2008;Tariq et al 2009). The P2Y5 was recently deciphered as key regulator of the hair follicle development.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to these four autosomal dominant forms of hereditary hypotrichosis, six isolated autosomal recessive forms have been mapped on diVerent human chromosomes. Congenital atrichia (MIM 203655), characterized by complete absence of scalp and body hair and appearance of papules mostly on scalp, has been reported to result from mutations in hairless (HR, MIM 225060) Cichon et al 1998) gene mapped on chromosome 8p21 Nothen et al 1998 (Aslam et al 2004) and LAH3 (MIM 611452) on 13q14.11-q21.32 (Wali et al 2007b) have been shown to result from the mutations in desmoglein 4 (DSG4, MIM 607892) (Kljuic et al 2003;RaWq et al 2004), lipase-H (LIPH, MIM 607365) (Kazantseva et al 2006;Ali et al 2007) and G-protein-coupled receptor (P2RY5, MIM 609239) gene (Pasternack et al 2008;Shimomura et al 2008;Azeem et al 2008;Tariq et al 2009), respectively. Patients with these three forms of localized hereditary hypotrichosis show either complete absence or wooly hair on scalp, sparse eyebrows and eyelashes, and sparse to absent body hair (Wali et al 2007b;Pasternack et al 2008;Shimomura et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Genetic mapping of a novel hypotrichosis locus to chromosome 7p21.3–p22.3 in a Pakistani family and screening of the candidate genes

et al. 2010

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Hereditary hypotrichosis is a heterogeneous group of inherited hair loss disorders characterized by diffused or localized thinning or absence of hair affecting scalp, eyebrows and eyelashes, and other body parts. Over the past few years, at least four autosomal dominant and six autosomal recessive forms of hypotrichosis have been described. All these ten forms of hypotrichosis have been mapped on different human chromosomes and the corresponding genes have been identified in most of these cases. In the present study, we have described a six-generation Pakistani consanguineous family with an autosomal recessive transmission of hereditary hypotrichosis. All the five affected individuals of the family showed complete absence of scalp hair and sparse eyebrows and eyelashes. They were born with complete absence of scalp hairs. Facial hair of beard and mustaches were present in all the affected adult male individuals. Papules were observed only on scalp of the affected individuals. A scalp biopsy from an affected individual showed markedly reduced number of hair follicles. Human genome scan using polymorphic microsatellite markers mapped the disease locus on chromosome 7p21.3-p22.3, flanked by markers D7S1532 and D7S3047. A maximum two-point LOD score of 4.74 (theta = 0.00) was obtained at marker D7S481. The linkage interval spans 15.69 cM, which corresponds to 6.59 Mb according to the sequence-based physical map (Build 36.2). Mutation analysis of five potential candidate genes (GNA12, FOXK1, DAGLB, ZNF12, ACTB), located in the linkage interval, did not reveal any functional sequence variant.

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“…The isolated hair loss disorders with variable clinical features, segregate either in autosomal dominant or recessive pattern [9]. Over the past few years, five genes including hairless (HR, MIM 225060) [2,11], desmoglein-4 (DSG4, MIM 607892) [25,43], lipase-H (LIPH, MIM 607365) [4,22,30], lysophosphatidic acid receptor 6 (LPAR6/P2RY5, MIM 609239) [7,34,36,39,42], and desmocollin-3 (DSC3, MIM 600271) [6] associated with the isolated (non-syndromic) forms of hair loss disorders have been characterized. In syndromic form of hair loss disorders, hair loss is associated with other abnormalities including impaired sweating, nail dystrophy, deformed or absent teeth, mental retardation, etc.…”

Section: Introductionmentioning

confidence: 99%

A novel homozygous variant in the dsp gene underlies the first case of non-syndromic form of alopecia

et al. 2015

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Autosomal recessive forms of hair loss (alopecia) disorders have previously been associated with variants in at least five different genes including hairless (HR), desmoglein-4 (DSG4), desmocollin-3 (DSC3), lipase-H (LIPH), and lysophosphatidic acid receptor 6 (LPAR6). Here, we report the first familial case of alopecia resulting from a novel homozygous variant in the DSP gene. Since previous reports indicated the presence of heart abnormalities in patients carrying variants in the DSP gene; therefore, the echocardiographic evaluations of all affected members were performed. The results clearly excluded the presence of any form of heart abnormality in patients of the present family. Human genome scan mapped a disease locus on chromosome 6p25.1-p23, harboring DSP gene. Sequence analysis identified a novel homozygous missense variant [c.1493C > T (p.Pro498Leu)] in the DSP gene as the underlying genetic cause of non-syndromic alopecia in the family. The transition alters the completely conserved Pro498 residue in the SH3 domain of plakin that contributes to the stability and rigidity of this subfamily of spectrin repeats (SRs) containing proteins. Our study strengthens the evidence that hereditary hair loss disorders are genetically heterogeneous and imply that isolated form of alopecia is allelic with cardiocutaneous syndromes.

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Mutations in theP2RY5gene underlie autosomal recessive hypotrichosis in 13 Pakistani families

Abstract: Mutations revealed in the present study extend the body of evidence implicating the P2RY5 gene in the pathogenesis of human hereditary hair loss.

Cited by 19 publications

References 16 publications

Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families

Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families

Genetic mapping of a novel hypotrichosis locus to chromosome 7p21.3–p22.3 in a Pakistani family and screening of the candidate genes

A novel homozygous variant in the dsp gene underlies the first case of non-syndromic form of alopecia

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