{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tasdelen E"],"funding":["National Institute of Neurological Disorders and Stroke","International Rett Syndrome Foundation","Ankara Universitesi","National Heart, Lung, and Blood Institute","NHGRI NIH HHS","NINDS NIH HHS","National Institutes of Health","National Human Genome Research Institute","NIGMS NIH HHS","Muscular Dystrophy Association"],"pagination":["2153-2161"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9197852"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["188(7)"],"pubmed_abstract":["Hereditary sensory and autonomic neuropathy type 2B (HSAN2B) is a rare autosomal recessive peripheral neuropathy caused by biallelic variants in RETREG1 (formerly FAM134B). HSAN2B is characterized by sensory impairment resulting in skin ulcerations, amputations, and osteomyelitis as well as variable weakness, spasticity, and autonomic dysfunction. Here, we report four affected individuals with recurrent osteomyelitis, ulceration, and amputation of hands and feet, sensory neuropathy, hyperhidrosis, urinary incontinence, and renal failure from a family without any known shared parental ancestry. Due to the history of chronic recurrent multifocal osteomyelitis and microcytic anemia, a diagnosis of Majeed syndrome was considered; however, sequencing of LPIN2 was negative. Family-based exome sequencing (ES) revealed a novel homozygous ultrarare RETREG1 variant NM_001034850.2:c.321G>A;p.Trp107Ter. Electrophysiological studies of the proband demonstrated axonal sensorimotor neuropathy predominantly in the lower extremities. Consistent with the lack of shared ancestry, the coefficient of inbreeding calculated from ES data was low (F = 0.002), but absence of heterozygosity (AOH) analysis demonstrated a 7.2 Mb AOH block surrounding the variant consistent with a founder allele. Two of the four affected individuals had unexplained renal failure which has not been reported in HSAN2B cases to date. Therefore, this report describes a novel RETREG1 founder allele and suggests renal failure may be an unrecognized feature of the RETREG1-disease spectrum."],"journal":["American journal of medical genetics. Part A"],"pubmed_title":["Novel RETREG1 (FAM134B) founder allele is linked to HSAN2B and renal disease in a Turkish family."],"pmcid":["PMC9197852"],"funding_grant_id":["U54HG003273","UM1 HG006542","U54 HG003273","R35 NS105078","K08 HG008986","T32 GM007526","512848","T32 GM007526‐42","R35NS105078","3701‐1","18B0230002","873841"],"pubmed_authors":["Jhangiani SN","Posey JE","Calame DG","Gibbs RA","Tasdelen E","Marafi D","Herman I","Coban-Akdemir Z","Altıparmak T","Pehlivan D","Fatih JM","Kutlay NY","Akay G","Du H","Lupski JR","Mitani T"],"additional_accession":[]},"is_claimable":false,"name":"Novel RETREG1 (FAM134B) founder allele is linked to HSAN2B and renal disease in a Turkish family.","description":"Hereditary sensory and autonomic neuropathy type 2B (HSAN2B) is a rare autosomal recessive peripheral neuropathy caused by biallelic variants in RETREG1 (formerly FAM134B). HSAN2B is characterized by sensory impairment resulting in skin ulcerations, amputations, and osteomyelitis as well as variable weakness, spasticity, and autonomic dysfunction. Here, we report four affected individuals with recurrent osteomyelitis, ulceration, and amputation of hands and feet, sensory neuropathy, hyperhidrosis, urinary incontinence, and renal failure from a family without any known shared parental ancestry. Due to the history of chronic recurrent multifocal osteomyelitis and microcytic anemia, a diagnosis of Majeed syndrome was considered; however, sequencing of LPIN2 was negative. Family-based exome sequencing (ES) revealed a novel homozygous ultrarare RETREG1 variant NM_001034850.2:c.321G>A;p.Trp107Ter. Electrophysiological studies of the proband demonstrated axonal sensorimotor neuropathy predominantly in the lower extremities. Consistent with the lack of shared ancestry, the coefficient of inbreeding calculated from ES data was low (F = 0.002), but absence of heterozygosity (AOH) analysis demonstrated a 7.2 Mb AOH block surrounding the variant consistent with a founder allele. Two of the four affected individuals had unexplained renal failure which has not been reported in HSAN2B cases to date. Therefore, this report describes a novel RETREG1 founder allele and suggests renal failure may be an unrecognized feature of the RETREG1-disease spectrum.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2024-11-21T05:46:12.903Z","creation":"2024-11-21T05:46:12.903Z"},"accession":"S-EPMC9197852","cross_references":{"pubmed":["35332675"],"doi":["10.1002/ajmg.a.62727"]}}