| 제목 |
Hereditary sensory and autonomic neuropathy 2B caused by a RETREG1 mutation and uniparental disomy 5 |
| 소속 |
Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Department of Rehabilitation Medicine1, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Department of Rehabilitation Medicine2 |
| 저자 |
Young-Ah Choi1, Dae-Hyun Jang1†, Dong-Woo Lee1, Jaewon Kim1*, Geun-Young Park2 |
Introduction: To Date, a total of eight families and five pathogenic variants related hereditary sensory and autonomic neuropathy (HSAN) 2B due to RETREG1 mutation have been reported since Kurth et al. first reported four families in 2009. HSAN 2B is characterized by progressive sensory deficit, and variable autonomic and motor involvement. Because the reported RETREG1 mutations are rare, there is no clear description of the phenotype of HSAN 2B. Here, we describe a novel frameshift mutation (c.765dupT/p.Gly256TrpfsTer7) of the RETREG1 and paternal uniparental isodisomy 5 in a patient diagnosed as having HSAN 2B.
Case: The proband was a 22-year-old female who visited our clinic for evaluation because of a sensory disturbance on both lower extremities and unstable gait. The patient is from a non-consanguineous Korean family and there was no familial history of hereditary disorders. She had a normal birth history and developmental milestone. Her symptoms had begun around ten years of age and gradually progressed. The patient exhibited a decreased pain, temperature, touch, vibration and position sense on the both lower extremities, and an ulcer on left toe which lasted more than a year and healed recently (Fig 1-A). She had mild lower extremities distal motor weakness (MRC 4), spasticity, and increased deep tendon reflex on the both lower extremities. She had normal intelligence and no autonomic symptoms. Nerve conduction study showed a sensory more than motor axonal polyneuropathy and sympathetic skin response was impaired on both sole. The multi-gene panel study related with neuromuscular disorders which was previously reported by us was performed. We found a frameshift homozygous variation in the patient’s RETREG1: c.765dupT/p.Gly256TrpfsTer7, which is a novel variation. However, of patient’s parents, only the father was identified as carrier for the variation on the Sanger sequencing tests (Fig 1-B). Furthermore, SNP array was performed in the patient and her parents, revealed a paternal uniparental disomy 5. (Fig 1-C and D)
Discussion: We have summarized the clinical features of our case and all the families reported previously in table 1. All cases have similar characteristics which are early onset (1st - 2nd decade), progressive sensory disturbance, distal motor weakness, skin ulcer, and/or spasticity, variable autonomic involvement. We reported a case with the patient diagnosed as having HSAN 2B caused by a novel frameshift mutation (c.765dupT/p.Gly256TrpfsTer7) of the RETREG1 and paternal uniparental isodisomy 5 in a non-consanguineous family. Clinicians should be aware that autosomal recessive disorders can be occurred by uniparental disomy in a non-consanguineous family.
|
|
Fig 1. (A) Left toe ulcer, (B) Chromotographies of RETREG1 gene, (C) SNP array, (D) Pedigree
Clinical features of our case and all the families with HSAN 2B reported previously
|
