Chen_2013_Hum.Mutat_34_1672

Reference

Title : Two Novel Mutations in ABHD12: Expansion of the Mutation Spectrum in PHARC and Assessment of Their Functional Effects - Chen_2013_Hum.Mutat_34_1672
Author(s) : Chen DH , Naydenov A , Blankman JL , Mefford HC , Davis M , Sul Y , Barloon AS , Bonkowski E , Wolff J , Matsushita M , Smith C , Cravatt BF , Mackie K , Raskind WH , Stella N , Bird TD
Ref : Hum Mutat , 34 :1672 , 2013
Abstract : PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts) is a recently described autosomal-recessive neurodegenerative disease caused by mutations in the alpha-beta-hydrolase domain-containing 12 gene (ABHD12). Only five homozygous ABHD12 mutations have been reported and the pathogenesis of PHARC remains unclear. We evaluated a woman who manifested short stature as well as the typical features of PHARC. Sequence analysis of ABHD12 revealed a novel heterozygous c.1129A>T (p.Lys377*) mutation. Targeted comparative genomic hybridization detected a 59-kb deletion that encompasses exon 1 of ABHD12 and exons 1-4 of an adjacent gene, GINS1, and includes the promoters of both genes. The heterozygous deletion was also carried by the patient's asymptomatic mother. Quantitative reverse transcription-PCR demonstrated approximately 50% decreased expression of ABHD12 RNA in lymphoblastoid cell lines from both individuals. Activity-based protein profiling of serine hydrolases revealed absence of ABHD12 hydrolase activity in the patient and 50% reduction in her mother. This is the first report of compound heterozygosity in PHARC and the first study to describe how a mutation might affect ABHD12 expression and function. The possible involvement of haploinsufficiency for GINS1, a DNA replication complex protein, in the short stature of the patient and her mother requires further studies.
ESTHER : Chen_2013_Hum.Mutat_34_1672
PubMedSearch : Chen_2013_Hum.Mutat_34_1672
PubMedID: 24027063
Gene_locus related to this paper: human-ABHD12

Related information

Gene_locus related to this paper: human-ABHD12

Citations formats

Chen DH, Naydenov A, Blankman JL, Mefford HC, Davis M, Sul Y, Barloon AS, Bonkowski E, Wolff J, Matsushita M, Smith C, Cravatt BF, Mackie K, Raskind WH, Stella N, Bird TD (2013)
Two Novel Mutations in ABHD12: Expansion of the Mutation Spectrum in PHARC and Assessment of Their Functional Effects
Hum Mutat 34 :1672

Chen DH, Naydenov A, Blankman JL, Mefford HC, Davis M, Sul Y, Barloon AS, Bonkowski E, Wolff J, Matsushita M, Smith C, Cravatt BF, Mackie K, Raskind WH, Stella N, Bird TD (2013)
Hum Mutat 34 :1672