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Wasim Ahmad - One of the best experts on this subject based on the ideXlab platform.
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mutations in the lipase h gene causing autosomal recessive Hypotrichosis and woolly hair
Australasian Journal of Dermatology, 2015Co-Authors: Sabba Mehmood, Ghazanfar Ali, Muhammad Ansar, Abid Jan, Muhammad Ayub, Dost Muhammad, Farooq Ahmad, Hina Mir, Muhammad Younus, Wasim AhmadAbstract:Hypotrichosis is characterised by sparse scalp hair, sparse to absent eyebrows and eyelashes, or absence of hair from other parts of the body. In few cases, the condition is associated with tightly curled woolly scalp hair. The present study searched for disease-causing sequence variants in the genes in four Pakistani lineal consanguineous families exhibiting features of Hypotrichosis or woolly hair. A haplotype analysis established links in all four families to the LIPH gene located on chromosome 3q27.2. Subsequently, sequencing LIPH identified a novel non-sense mutation (c.328C>T; p.Arg110*) in one and a previously reported 2-bp deletion mutation (c.659_660delTA, p.Ile220ArgfsX29) in three other families.
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a novel deletion mutation in the dsg4 gene underlies autosomal recessive Hypotrichosis with variable phenotype in two unrelated consanguineous families
Clinical and Experimental Dermatology, 2015Co-Authors: Asmat Ullah, Syed Irfan Raza, Raja Hussain Ali, A K Naveed, Abid Jan, S D A Rizvi, Rabab Satti, Wasim AhmadAbstract:Summary Background Autosomal recessive Hypotrichosis is a rare human hereditary disorder presenting as sparse scalp hair or as woolly hair occurring on various parts of the body. Various forms of isolated Hypotrichosis have been reported to date. Mutations in at least 11 genes have been reported to cause Hypotrichosis. Aims To investigate the clinical and genetic basis of autosomal recessive Hypotrichosis in two unrelated consanguineous families. Methods Genotyping by highly polymorphic microsatellite markers established linkage in both families to the DSG4 gene on chromosome 18q21. PCR amplification of exons and intron–exon borders of the DSG4 gene was performed, and the products sequenced to search for disease-causing sequence variants. Results Clinical investigation revealed typical Hypotrichosis in the affected members of one family, while other affected members showed presence of monilethrix-like scalp hair. Sequence analysis of DSG4 revealed a novel deletion mutation (c.85-1_191del) in the affected subjects of both families. Conclusions This study further extends the body of evidence that mutations in the DSG4 gene result in both Hypotrichosis and monilethrix-like scalp hair.
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in silico analysis of missense mutations in lpar6 reveals abnormal phospholipid signaling pathway leading to Hypotrichosis
PLOS ONE, 2014Co-Authors: Syed Irfan Raza, Wasim Ahmad, Raja Hussain Ali, Abid Jan, Dost Muhammad, Mubashir Hassan, Sajid RashidAbstract:Autosomal recessive Hypotrichosis is a rare genetic irreversible hair loss disorder characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. The study, presented here, established genetic linkage in four families showing similar phenotypes to lysophosphatidic acid receptor 6 (LPAR6) gene on chromosome 13q14.11-q21.32. Subsequently, sequence analysis of the gene revealed two previously reported missense mutations including p.D63V in affected members of one and p.I188F in three other families. Molecular modeling and docking analysis was performed to investigate binding of a ligand oleoyl-L-alpha-lysophosphatidic acid (LPA) to modeled protein structures of normal and mutated (D63V, G146R, I188F, N248Y, S3T, L277P) LPAR6 receptors. The mutant receptors showed a complete shift in orientation of LPA at the binding site. In addition, hydropathy analysis revealed a significant change in the membrane spanning topology of LPAR6 helical segments. The present study further substantiated involvement of LPAR6-LPA signaling in the pathogenesis of Hypotrichosis/woolly hair and provided additional insight into the molecular mechanism of hair development.
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digenic inheritance of an autosomal recessive Hypotrichosis in two consanguineous pedigrees
Clinical Genetics, 2011Co-Authors: Sulman Basit, Abdul Wali, Musharraf Jelani, Abdul Aziz, Noor Muhammad, Wasim AhmadAbstract:Hypotrichosis is a human hereditary hair loss disorder in which affected individuals show sparse to complete absence of hair on scalp and/or on different body parts. To date, at least eight isolated autosomal recessive and dominant forms of Hypotrichosis loci have been mapped on different human chromosomes, and the corresponding genes have been identified. Detailed clinical and molecular studies were undertaken of the hereditary Hypotrichosis observed in the two consanguineous families (A and B) presented here. Human genome scan, using >500 highly polymorphic microsatellite markers, identified equal evidence of linkage of the Hypotrichosis phenotype on chromosomes 12q21.2-q22 and 16q21-q23.1 in both the families. The novel Hypotrichosis locus on chromosome 12q21.2-q22 spans 16.3 cM (17.62 Mb), flanked by markers D12S326 and D12S101. At this locus, maximum multipoint logarithm of the odds ratio (LOD) scores of 3.68 and 3.31 were obtained in families A and B, respectively. The second Hypotrichosis locus on chromosome 16q21-q23.1, identified in the two families, spans 5.58 cM (8.28 Mb) and is flanked by markers D16S3031 and D16S512. Maximum multipoint LOD scores of 3.17 and 3.31 were obtained with markers mapped at this locus in families A and B, respectively. DNA sequence analysis of six candidate genes (PLEKHG7, SLC6A15, VEZT, DUSP6, KERA and KITLG), located in the linkage interval on chromosome 12q21.2-q22, failed to detect potential sequence variants in the affected individuals of the two families. However, DNA sequence analysis of CDH3 gene, located on chromosome 16q21-q23.1, detected a single base pair homozygous insertion (c.1024_1025insG and p.342insGfsX345) in exon 9 in family A and deletion of four base pair (c.1859_1862delCTCT and p.620delSfsX629) in exon 13 in family B. We described for the first time digenic inheritance of an autosomal recessive Hypotrichosis phenotype in two unlinked loci on chromosomes 12q21.2-q22 and 16q21-q23.1 in two unrelated consanguineous Pakistani families.
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novel missense mutations in lipase h liph gene causing autosomal recessive Hypotrichosis lah2
Journal of Dermatological Science, 2009Co-Authors: Gul Naz, Bushra Khan, Ghazanfar Ali, Zahid Azeem, Abdul Wali, Muhammad Ansar, Wasim AhmadAbstract:Abstract Background Autosomal recessive hypotrishosis (LAH2) is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. However, affected male individuals have normal beard hair. Mutations in lipase H ( LIPH ) gene, located on chromosome 3q26.33, have been shown to be responsible for LAH2 type of Hypotrichosis. Objectives To search for pathogenic mutations in LIPH gene at LAH2 locus in Pakistani families demonstrating autosomal recessive Hypotrichosis. Methods In the present study we have ascertained two large unrelated consanguineous Pakistani families (A and B) inherited autosomal recessive form of Hypotrichosis. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive Hypotrichosis loci LAH1, LAH2 and LAH3. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene at LAH2 locus on chromosome 3q26.33. These families were then subjected to direct sequencing of the LIPH gene. Results Sequence analysis of the LIPH gene revealed two novel missense mutations (c.2T > C; p.M1T and c.322T > C; p.W108R) in the two families. Conclusion The mutations reported here are the first missense mutations identified in the LIPH gene, which extend the body of evidences implicating the LIPH gene in the pathogenesis of human hereditary hair loss.
Angela M Christiano - One of the best experts on this subject based on the ideXlab platform.
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splice site mutations in the p cadherin gene underlie Hypotrichosis with juvenile macular dystrophy
Dermatology, 2010Co-Authors: Yutaka Shimomura, Muhammad Wajid, Mazen Kurban, Angela M ChristianoAbstract:Background: Hypotrichosis with juvenile macular dystrophy (HJMD; OMIM 601553) is a rare autosomal recessive disorder characterized by Hypotrichosis with short scalp hair and progres
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founder mutations in the lipase h gene in families with autosomal recessive woolly hair Hypotrichosis
Journal of Investigative Dermatology, 2009Co-Authors: Yutaka Shimomura, Muhammad Wajid, Abraham Zlotogorski, Young Jin Lee, Robert H Rice, Angela M ChristianoAbstract:Autosomal-recessive woolly hair (ARWH)/Hypotrichosis is a hereditary hair disorder which is characterized by tightly curled hair and is associated with sparse hair. ARWH can be caused by mutations in the P2RY5 or lipase H (LIPH) gene. Disruption of either gene results in phenotypes with features of both wooly hair (WH) and Hypotrichosis. In this study, we identified two Guyanese families with ARWH. Both families are of recent Indian descent. Mutation analysis resulted in the identification of mutations in the LIPH gene in both families. Affected individuals in the first family carry compound heterozygous mutations Ex7_8del and 1303_1309dupGAAAACG in the LIPH gene, while those in the second family have a homozygous mutation 659_660delTA in the LIPH gene. The mutations Ex7_8del and 659_660delTA were identified earlier in several Pakistani families with ARWH. Haplotype analysis using microsatellite markers close to the LIPH gene defined a founder haplotype shared in families from Pakistan and Guyana. Proteomic analysis of hair shaft samples from one of the families revealed no substantial changes among the proteins identified, indicating that the syndrome does not involve global alterations in protein expression. Our results further suggest a crucial role of LIPH gene in hair growth.
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autosomal recessive woolly hair with Hypotrichosis caused by a novel homozygous mutation in the p2ry5 gene
Experimental Dermatology, 2009Co-Authors: Yutaka Shimomura, Maria C Garzon, Leonard Kristal, Lawrence Shapiro, Angela M ChristianoAbstract:During the last decade, several causative genes for hereditary hair diseases have been identified, which have disclosed the molecular mechanisms involved in hair follicle morphogenesis and cycling. We and others recently reported that mutations in the P2RY5 gene, encoding an orphan G protein-coupled receptor, underlie autosomal recessive woolly hair (WH)/Hypotrichosis. Although these findings clearly reveal the involvement of P2RY5 mutations in hereditary hair diseases, the clinical manifestations of P2RY5 mutations have not completely been elucidated because of limited information to date. In this study, we ascertained a consanguineous family of Iranian origin with an affected girl showing sparse and hypopigmented scalp hair. She exhibited the WH phenotype with normal hair density at birth, but progressed with age to develop Hypotrichosis. Direct sequencing analysis resulted in the identification of a novel homozygous mutation in the P2RY5 gene of the patient, which results in a non-conservative amino acid change, G146R, at the protein level. Our findings extend the mutation spectrum of P2RY5 mutations, and further support a crucial role of P2Y5 in hair growth in humans.
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mutations in the lipase h gene underlie autosomal recessive woolly hair Hypotrichosis
Journal of Investigative Dermatology, 2009Co-Authors: Yutaka Shimomura, Muhammad Wajid, Lawrence Shapiro, Lynn Petukhova, Angela M ChristianoAbstract:Woolly hair (WH) is characterized by the presence of fine and tightly curled hair. WH can appear as a symptom of some systemic diseases, or without associated findings (nonsyndromic WH). Nonsyndromic WH is known to be inherited as either an autosomal-dominant (OMIM 194300) or recessive (ARWH; OMIM 278150) trait. In this study, we identified 11 consanguineous families of Pakistani origin with ARWH, as well as associated features including sparse and hypopigmented hair shafts. We first checked for mutations in the P2RY5 gene, which encodes an orphan G-protein-coupled receptor that we recently identified as a cause of ARWH. However, none of the 11 families had mutations in the P2RY5 gene. To identify the disease locus, we performed linkage studies in one of these families using the Affymetrix 10K array, and identified a region of suggestive linkage on chromosome 3q27. This region contains the lipase H (LIPH) gene which has been recently shown to underlie an autosomal-recessive form of Hypotrichosis. Mutation analysis resulted in the identification of a total of 5 pathogenic mutations in the LIPH of all 11 families analyzed. These results show that LIPH is a second causative gene for ARWH/Hypotrichosis, giving rise to a phenotype clinically indistinguishable from P2RY5 mutations.
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genome wide linkage analysis of an autosomal recessive Hypotrichosis identifies a novel p2ry5 mutation
Genomics, 2008Co-Authors: Lynn Petukhova, Yutaka Shimomura, Amalia Martinezmir, Lawrence Shapiro, Edilson C Sousa, Anna Vitebsky, Lina Gomes Dos Santos, Chad Haynes, Derek Gordon, Angela M ChristianoAbstract:While there have been significant advances in understanding the genetic etiology of human hair loss over the previous decade, there remain a number of hereditary disorders for which a causative gene has yet to be identified. We studied a large, consanguineous Brazilian family that presented with woolly hair at birth that progressed to severe Hypotrichosis by the age of 5, in which 6 of the 14 offspring were affected. After exclusion of known candidate genes, a genome-wide scan was performed to identify the disease locus. Autozygosity mapping revealed a highly significant region of extended homozygosity (lod score of 10.41) that contained a haplotype with a linkage lod score of 3.28. Results of these two methods defined a 9-Mb region on chromosome 13q14.11-q14.2. The interval contains the P2RY5 gene, in which we recently identified pathogenic mutations in several families of Pakistani origin affected with autosomal recessive woolly and sparse hair. After the exclusion of several other candidate genes, we sequenced the P2RY5 gene and identified a homozygous mutation (C278Y) in all affected individuals in this family. Our findings show that mutations in P2RY5 display variable expressivity, underlying both Hypotrichosis and woolly hair, and underscore the essential role of P2RY5 in the tissue integrity and maintenance of the hair follicle.
Yutaka Shimomura - One of the best experts on this subject based on the ideXlab platform.
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two cases of severe congenital Hypotrichosis caused by compound heterozygous mutations in the lss gene
Journal of Dermatology, 2021Co-Authors: Mami Murata, Ryota Hayashi, Yoshio Kawakami, Shin Morizane, Yutaka ShimomuraAbstract:It has recently been shown that bi-allelic mutations in the lanosterol synthase (LSS) gene, which was originally reported as a causative gene for congenital cataracts, underlie a non-syndromic form of Hypotrichosis. Furthermore, it has also been revealed that mutations in the LSS gene can cause syndromic forms of Hypotrichosis. To date, however, clear genotype-phenotype correlations have not completely been characterized. In this study, we identified two Japanese patients who had severe congenital Hypotrichosis without any other associated findings. Their scalp hairs were extremely short and thin, and were able to be plucked easily. Observation of the plucked hairs showed aberrantly-miniaturized anagen hair follicles. Genetic analysis demonstrated that both patients carried bi-allelic mutations in the LSS gene in a compound heterozygote state. Our findings further underscore the crucial roles of the LSS gene in hair follicle development and hair growth in humans.
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autosomal recessive Hypotrichosis with woolly hair caused by a mutation in the keratin 25 gene expressed in hair follicles
Journal of Investigative Dermatology, 2016Co-Authors: Nikolay Zernov, Yutaka Shimomura, Mikhail Skoblov, Andrey V Marakhonov, Tatyana A Vasilyeva, Fedor A Konovalov, Anna V Abrukova, R A ZinchenkoAbstract:Hypotrichosis is an abnormal condition characterized by decreased hair density and various defects in hair structure and growth patterns. In particular, in woolly hair, Hypotrichosis is characterized by a tightly curled structure and abnormal growth. In this study, we present a detailed comparative examination of individuals affected by autosomal-recessive Hypotrichosis (ARH), which distinguishes two types of ARH. Earlier, we demonstrated that exon 4 deletion in the lipase H gene caused an ARH (Hypotrichosis 7; MIM: 604379) in populations of the Volga-Ural region of Russia. Screening for this mutation in all affected individuals revealed its presence only in the group with the Hypotrichosis 7 phenotype. Other patients formed a separate group of woolly hair-associated ARH, with a homozygous missense mutation c.712G>T (p.Val238Leu) in a highly conserved position of type I keratin KRT25 (K25). Haplotype analysis indicated a founder effect. An expression study in the HaCaT cell line demonstrated a deleterious effect of the p.Val238Leu mutation on the formation of keratin intermediate filaments. Hence, we have identified a previously unreported missense mutation in the KRT25 gene causing ARH with woolly hair.
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splice site mutations in the p cadherin gene underlie Hypotrichosis with juvenile macular dystrophy
Dermatology, 2010Co-Authors: Yutaka Shimomura, Muhammad Wajid, Mazen Kurban, Angela M ChristianoAbstract:Background: Hypotrichosis with juvenile macular dystrophy (HJMD; OMIM 601553) is a rare autosomal recessive disorder characterized by Hypotrichosis with short scalp hair and progres
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founder mutations in the lipase h gene in families with autosomal recessive woolly hair Hypotrichosis
Journal of Investigative Dermatology, 2009Co-Authors: Yutaka Shimomura, Muhammad Wajid, Abraham Zlotogorski, Young Jin Lee, Robert H Rice, Angela M ChristianoAbstract:Autosomal-recessive woolly hair (ARWH)/Hypotrichosis is a hereditary hair disorder which is characterized by tightly curled hair and is associated with sparse hair. ARWH can be caused by mutations in the P2RY5 or lipase H (LIPH) gene. Disruption of either gene results in phenotypes with features of both wooly hair (WH) and Hypotrichosis. In this study, we identified two Guyanese families with ARWH. Both families are of recent Indian descent. Mutation analysis resulted in the identification of mutations in the LIPH gene in both families. Affected individuals in the first family carry compound heterozygous mutations Ex7_8del and 1303_1309dupGAAAACG in the LIPH gene, while those in the second family have a homozygous mutation 659_660delTA in the LIPH gene. The mutations Ex7_8del and 659_660delTA were identified earlier in several Pakistani families with ARWH. Haplotype analysis using microsatellite markers close to the LIPH gene defined a founder haplotype shared in families from Pakistan and Guyana. Proteomic analysis of hair shaft samples from one of the families revealed no substantial changes among the proteins identified, indicating that the syndrome does not involve global alterations in protein expression. Our results further suggest a crucial role of LIPH gene in hair growth.
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autosomal recessive woolly hair with Hypotrichosis caused by a novel homozygous mutation in the p2ry5 gene
Experimental Dermatology, 2009Co-Authors: Yutaka Shimomura, Maria C Garzon, Leonard Kristal, Lawrence Shapiro, Angela M ChristianoAbstract:During the last decade, several causative genes for hereditary hair diseases have been identified, which have disclosed the molecular mechanisms involved in hair follicle morphogenesis and cycling. We and others recently reported that mutations in the P2RY5 gene, encoding an orphan G protein-coupled receptor, underlie autosomal recessive woolly hair (WH)/Hypotrichosis. Although these findings clearly reveal the involvement of P2RY5 mutations in hereditary hair diseases, the clinical manifestations of P2RY5 mutations have not completely been elucidated because of limited information to date. In this study, we ascertained a consanguineous family of Iranian origin with an affected girl showing sparse and hypopigmented scalp hair. She exhibited the WH phenotype with normal hair density at birth, but progressed with age to develop Hypotrichosis. Direct sequencing analysis resulted in the identification of a novel homozygous mutation in the P2RY5 gene of the patient, which results in a non-conservative amino acid change, G146R, at the protein level. Our findings extend the mutation spectrum of P2RY5 mutations, and further support a crucial role of P2Y5 in hair growth in humans.
Ghazanfar Ali - One of the best experts on this subject based on the ideXlab platform.
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mutations in the lipase h gene causing autosomal recessive Hypotrichosis and woolly hair
Australasian Journal of Dermatology, 2015Co-Authors: Sabba Mehmood, Ghazanfar Ali, Muhammad Ansar, Abid Jan, Muhammad Ayub, Dost Muhammad, Farooq Ahmad, Hina Mir, Muhammad Younus, Wasim AhmadAbstract:Hypotrichosis is characterised by sparse scalp hair, sparse to absent eyebrows and eyelashes, or absence of hair from other parts of the body. In few cases, the condition is associated with tightly curled woolly scalp hair. The present study searched for disease-causing sequence variants in the genes in four Pakistani lineal consanguineous families exhibiting features of Hypotrichosis or woolly hair. A haplotype analysis established links in all four families to the LIPH gene located on chromosome 3q27.2. Subsequently, sequencing LIPH identified a novel non-sense mutation (c.328C>T; p.Arg110*) in one and a previously reported 2-bp deletion mutation (c.659_660delTA, p.Ile220ArgfsX29) in three other families.
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novel missense mutations in lipase h liph gene causing autosomal recessive Hypotrichosis lah2
Journal of Dermatological Science, 2009Co-Authors: Gul Naz, Bushra Khan, Ghazanfar Ali, Zahid Azeem, Abdul Wali, Muhammad Ansar, Wasim AhmadAbstract:Abstract Background Autosomal recessive hypotrishosis (LAH2) is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. However, affected male individuals have normal beard hair. Mutations in lipase H ( LIPH ) gene, located on chromosome 3q26.33, have been shown to be responsible for LAH2 type of Hypotrichosis. Objectives To search for pathogenic mutations in LIPH gene at LAH2 locus in Pakistani families demonstrating autosomal recessive Hypotrichosis. Methods In the present study we have ascertained two large unrelated consanguineous Pakistani families (A and B) inherited autosomal recessive form of Hypotrichosis. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive Hypotrichosis loci LAH1, LAH2 and LAH3. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene at LAH2 locus on chromosome 3q26.33. These families were then subjected to direct sequencing of the LIPH gene. Results Sequence analysis of the LIPH gene revealed two novel missense mutations (c.2T > C; p.M1T and c.322T > C; p.W108R) in the two families. Conclusion The mutations reported here are the first missense mutations identified in the LIPH gene, which extend the body of evidences implicating the LIPH gene in the pathogenesis of human hereditary hair loss.
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a novel deletion mutation in liph gene causes autosomal recessive Hypotrichosis lah2
Clinical Genetics, 2008Co-Authors: Musharraf Jelani, Ghazanfar Ali, Naveed Wasif, Wasim AhmadAbstract:Autosomal recessive Hypotrichosis is a rare hereditary disorder characterized by sparse hair on scalp and rest of the body of affected subjects. Recently, three clinically similar autosomal recessive forms of Hypotrichosis [localized autosomal recessive Hypotrichosis (LAH)1], LAH2 and LAH3 have been mapped on chromosomes 18q12.1, 3q27.3, and 13q14.11-q21.32, respectively. For these three loci, two genes DSG4 for LAH1 and LIPH for LAH2 have been identified. To date, only five mutations in DSG4 and two in LIPH genes have been reported. In this study, we have ascertained two large unrelated consanguineous Pakistani families with autosomal recessive form of Hypotrichosis. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene on chromosome 3q27. Sequence analysis of the gene in the affected subjects from both the families revealed a novel deletion mutation in exon 5 (c.659-660delTA) causing frameshift and downstream premature termination codon. All the three mutations identified in the LIPH gene, including the one in this study, are deletion mutations.
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localization of a novel autosomal recessive Hypotrichosis locus lah3 to chromosome 13q14 11 q21 32
Clinical Genetics, 2007Co-Authors: Abdul Wali, Ghazanfar Ali, Muhammad Salman Chishti, Muhammad Ayub, Masoom Yasinzai, Peter John, Wasim AhmadAbstract:Autosomal recessive Hypotrichosis is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. Previously, for this form of Hypotrichosis, two loci LAH (localized hereditary Hypotrichosis) and AH (autosomal recessive hereditary Hypotrichosis) have been mapped on chromosome 18q12.1 and 3q27.2, respectively. In the study presented here, we report the localization of a third locus for autosomal recessive form of Hypotrichosis in two large Pakistani families. The patients in the two families exhibited typical features of the hereditary Hypotrichosis. Genome scan using polymorphic microsatellite markers mapped the gene on chromosome 13q14.11-q21.32. A maximum combined two-point logarithm of odds (LOD) score of 4.79 at theta= 0.0 was obtained for several markers. Multipoint linkage analysis resulted in a maximum LOD score of 5.9, which further supports the linkage. Haplotype analysis defined the linkage interval of 17.35 cM flanked by markers D13S325 and D13S1231 according to the Rutgers combined linkage-physical map. This region contains 24.41 Mb according to the build 36 of the human genome sequence-based physical map.
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A mutation in the lipase H (LIPH) gene underlie autosomal recessive Hypotrichosis
Human Genetics, 2007Co-Authors: Ghazanfar Ali, Syed Irfan Raza, Muhammad Salman Chishti, Peter John, Wasim AhmadAbstract:Hereditary Hypotrichosis is a rare autosomal recessive disorder characterized by sparse hair on scalp and rest of the body of affected individuals. Two forms of such Hypotrichosis LAH and AH have been mapped on chromosome 18q12.1 and 3q27, respectively. Mutations in desmogelin 4 ( DSG4 ) gene have been reported to underlie LAH. Recently, a deletion mutation in Lipase H ( LIPH ) gene, located at AH locus, has been identified in two ethnic groups of Russian population. In the present study, a four generation Pakistani family with AH phenotype has been mapped to chromosome 3q27. Sequence analysis of candidate gene LIPH revealed a novel five base pair deletion mutation (c.346–350delATATA) in exon 2 of the gene leading to frameshift and downstream premature termination codon. The mutation reported in the family, presented here, is the second mutation identified in LIPH gene. The identification of a genetic defect in LIPH suggests that this enzyme regulates hair growth.
Thomas Besnard - One of the best experts on this subject based on the ideXlab platform.
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biallelic pathogenic variants in the lanosterol synthase gene lss involved in the cholesterol biosynthesis cause alopecia with intellectual disability a rare recessive neuroectodermal syndrome
Genetics in Medicine, 2019Co-Authors: Thomas Besnard, Natacha Sloboda, Sebastien Kury, Flora Breheret, Eva Trochu, Solene Conrad, Marie Vincent, Benjamin Cogne, Alice Goldenberg, X BalguerieAbstract:Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with Hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by Hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with early-onset epilepsy and other dermatological features. Through a multicenter international collaborative study, we identified LSS pathogenic variants in APMR individuals either by exome sequencing or LSS Sanger sequencing. Splicing defects were assessed by transcript analysis and minigene assay. We reported ten APMR individuals from six unrelated families with biallelic variants in LSS. We additionally identified one affected individual with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome.
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Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome.
Genetics in Medicine, 2019Co-Authors: Thomas Besnard, Natacha Sloboda, Sebastien Kury, Flora Breheret, Eva Trochu, Solene Conrad, Marie Vincent, Benjamin Cogne, Alice Goldenberg, Wallid DebAbstract:Purpose Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with Hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by Hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with early-onset epilepsy and other dermatological features. Methods Through a multicenter international collaborative study, we identified LSS pathogenic variants in APMR individuals either by exome sequencing or LSS Sanger sequencing. Splicing defects were assessed by transcript analysis and minigene assay. Results We reported ten APMR individuals from six unrelated families with biallelic variants in LSS. We additionally identified one affected individual with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. Conclusion In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome.