Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3)

Azeem, Zahid; Jelani, Musharraf; Naz, Gul; Tariq, Muhammad; Wasif, Naveed; Naqvi, Syed Kamran-ul-Hassan; Ayub, Muhammad; Yasinzai, Masoom; Aminuddin, Muhammad; Wali, Abdul; Ali, Ghazanfar; Chishti, Muhammad Salman; Ahmad, Wasim

doi:10.1007/s00439-008-0507-7

Cited by 36 publications

(49 citation statements)

References 10 publications

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“…The conditions used for amplification of the microsatellite markers were the same as described earlier (Azeem et al 2008).…”

Section: Extraction Of Genomic Dna and Genotypingmentioning

confidence: 99%

“…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: 98%

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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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“…The conditions used for amplification of the microsatellite markers were the same as described earlier (Azeem et al 2008).…”

Section: Extraction Of Genomic Dna and Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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

et al. 2010

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“…Likewise, the crystal structure of rhodopsin (7) suggests that the aspartic acid in TM2 makes a hydrogen bond with asparagine in TM1 and alanine in TM7; therefore, it too might contribute to the correct folding of GPCRs. Interestingly, single nucleotide polymorphisms of prolines in TM6 of rhodopsin (31) and the V2 vasopressin receptor (32,33) and aspartic acids in TM2 of the P2Y5/LPA6 receptor (34,35) and melanocortin 1 receptor (36) have been reported. Although precise analyses of these mutants have not been completed, these mutant receptors might be eliminated by the ER-associated degradation system because of their aberrant structures.…”

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confidence: 99%

Amino Acid Residues Critical for Endoplasmic Reticulum Export and Trafficking of Platelet-activating Factor Receptor

Hirota

Yasuda

Hashidate

et al. 2010

Journal of Biological Chemistry

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Several residues are conserved in the transmembrane domains (TMs) of G-protein coupled receptors. Here we demonstrate that a conserved proline, Pro 247 , in TM6 of platelet-activating factor receptor (PAFR) is required for endoplasmic reticulum (ER) export and trafficking after agonist-induced internalization. Alanine-substituted mutants of the conserved residues of PAFRs, including P247A, were retained in the ER. Because a PAFR antagonist, Y-24180, acted as a pharmacological chaperone to rescue ER retention, this retention is due to misfolding of PAFR. Methylcarbamyl (mc)-PAF, a PAFR agonist, did not increase the cell surface expression of P247A, even though another ER-retained mutant, D63A, was effectively trafficked. Signaling and accumulation of the receptors in the early endosomes were observed in the mc-PAF-treated P247A-expressing cells, suggesting that P247A was trafficked to the cell surface by mc-PAF, and thereafter disappeared from the surface due to aberrant trafficking, e.g. enhanced internalization, deficiency in recycling, and/or accelerated degradation. The aberrant trafficking was confirmed with a sortase-A-mediated method for labeling cell surface proteins. These results demonstrate that the conserved proline in TM6 is crucial for intracellular trafficking of PAFR.

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“…This included congenital atrichia (MIM 203655) at 8p21 Nothen et al 1998), localized hereditary hypotrichosis (LAH, MIM 607903) at 18q12.1 (Kljuic et al 2003;Rafique et al 2003), autosomal recessive hereditary hypotrichosis (LAH2, MIM 609167) at 3q27.2 (Aslam et al 2004), LAH3 (MIM 611452) at 13q14.11-q21.32 (Wali et al 2007a) and hereditary hypotrichosis with skin vesicles (MIM 613102) at 18q21.1 ). All these five conditions congenital atrichia, LAH1, LAH2, LAH3 and hereditary hypotrichosis with skin vesicles have been reported to result from mutations in hairless (HR, MIM 225060) Cichon et al 1998), desmoglein 4 (DSG4, MIM 607892) (Kljuic et al 2003;Rafiq et al 2004), lipase-H (LIPH, MIM 607365) (Kazantseva et al 2006;Ali et al 2007), G-protein coupledreceptor (P2RY5, MIM 609239) (Pasternack et al 2008;Shimomura et al 2008;Azeem et al 2008;Tariq et al 2009) and desmocollin-3 (DSC3, MIM 600271) ) genes, respectively. An autosomal dominant form of isolated hypotrichosis simplex of the scalp has been shown to result from mutations in corneodesmosin gene (CDSN, MIM 602593) (Levy-Nissenbau et al 2003).…”

Section: Introductionmentioning

confidence: 97%

Mapping of a novel autosomal recessive hypotrichosis locus on chromosome 10q11.23–22.3

et al. 2010

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Autosomal recessive hypotrichosis is a rare form of human genetic disorder characterized by sparse to absent hair on scalp and rest of the body of affected individuals. Over the past few years at least five autosomal recessive forms of hypotrichosis loci have been mapped on different human chromosomes. In the present study, we report localization of another novel autosomal recessive hypotrichosis locus on human chromosome 10q11.23-22.3 in a four generation consanguineous Pakistani family. All the four patients in the family showed typical features of hereditary hypotrichosis including sparse hair on the scalp and rest of the body. Human genome scan using highly polymorphic microsatellite markers mapped the disease locus to a large region on chromosome 10. This novel locus maps to 29.81 cM (28.5 Mb) region, flanked by markers D10S538 and D10S2327 on chromosome 10q11.23-22.3. A maximum multipoint LOD score of 3.26 was obtained with several markers in this region. DNA sequence analysis of exons and splice-junction sites of four putative candidate genes (P4HA1, ZNF365, ZMYND17, MYST4), located in the linkage interval, were sequenced but were negative for functional sequence variants.

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Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3)

Cited by 36 publications

References 10 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

Amino Acid Residues Critical for Endoplasmic Reticulum Export and Trafficking of Platelet-activating Factor Receptor

Mapping of a novel autosomal recessive hypotrichosis locus on chromosome 10q11.23–22.3

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