Biallelic mutations in the LPAR6 gene causing autosomal recessive wooly hair/hypotrichosis phenotype in five Pakistani families.
Computational Biology
Consanguinity
Female
Genes, Recessive
/ genetics
Hair
/ abnormalities
Hair Diseases
/ genetics
Humans
Hypotrichosis
/ genetics
Male
Mutation, Missense
Pakistan
Pedigree
Phenotype
Protein Structure, Secondary
/ genetics
Receptors, Lysophosphatidic Acid
/ chemistry
Receptors, Purinergic P2
/ chemistry
Sequence Homology, Amino Acid
Journal
International journal of dermatology
ISSN: 1365-4632
Titre abrégé: Int J Dermatol
Pays: England
ID NLM: 0243704
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
28
09
2018
revised:
25
02
2019
accepted:
11
04
2019
pubmed:
12
5
2019
medline:
18
12
2019
entrez:
12
5
2019
Statut:
ppublish
Résumé
Autosomal recessive wooly hair/hypotrichosis is an inherited disorder of hair characterized by less dense, short, and tightly curled hair on the scalp and sometimes less dense to complete absence of eyebrows and eyelashes. Autosomal recessive wooly hair/hypotrichosis phenotypes are mostly associated with pathogenic sequence variants in LIPH and LPAR6 genes. To find out the molecular basis of the disease, five families with autosomal recessive wooly hair/hypotrichosis were recruited for genetic analysis. Direct Sanger sequencing of LIPH and LPAR6 genes was carried out using BigDye chain termination chemistry. P2RY5 protein homology models were developed to study the effect of mutation on protein structure in a family having novel mutation. Sanger sequencing revealed a novel homozygous missense mutation (c.47A>T) in the LPAR6 gene in family A, while recurrent mutation (c.436G>A) was detected in the rest of the four families (B-E). Protein homology models for both native and mutant P2RY5 protein were developed to study the difference in subtle structural features because of Lys16Met (K16M) mutation. We observed that P2RY5 The molecular analysis further confirms the frequent involvement of LPAR6 in autosomal recessive wooly hair/hypotrichosis, while the bioinformatic study revealed that the missense mutation destabilizes the overall structure of P2RY5 protein.
Sections du résumé
BACKGROUND
BACKGROUND
Autosomal recessive wooly hair/hypotrichosis is an inherited disorder of hair characterized by less dense, short, and tightly curled hair on the scalp and sometimes less dense to complete absence of eyebrows and eyelashes. Autosomal recessive wooly hair/hypotrichosis phenotypes are mostly associated with pathogenic sequence variants in LIPH and LPAR6 genes.
METHODS
METHODS
To find out the molecular basis of the disease, five families with autosomal recessive wooly hair/hypotrichosis were recruited for genetic analysis. Direct Sanger sequencing of LIPH and LPAR6 genes was carried out using BigDye chain termination chemistry. P2RY5 protein homology models were developed to study the effect of mutation on protein structure in a family having novel mutation.
RESULTS
RESULTS
Sanger sequencing revealed a novel homozygous missense mutation (c.47A>T) in the LPAR6 gene in family A, while recurrent mutation (c.436G>A) was detected in the rest of the four families (B-E). Protein homology models for both native and mutant P2RY5 protein were developed to study the difference in subtle structural features because of Lys16Met (K16M) mutation. We observed that P2RY5
CONCLUSION
CONCLUSIONS
The molecular analysis further confirms the frequent involvement of LPAR6 in autosomal recessive wooly hair/hypotrichosis, while the bioinformatic study revealed that the missense mutation destabilizes the overall structure of P2RY5 protein.
Substances chimiques
LPAR4 protein, human
0
LPAR6 protein, human
0
Receptors, Lysophosphatidic Acid
0
Receptors, Purinergic P2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
946-952Subventions
Organisme : Higher Education Commission (HEC), Islamabad, Pakistan
ID : 20-2407/HEC/R&D/NRPU/14
Organisme : Higher Education Commission (HEC), Islamabad, Pakistan
ID : 20-4857/HEC/R&D/NRPU/14
Informations de copyright
© 2019 The International Society of Dermatology.