Clinical and molecular characteristics in three families with biallelic mutations in IGHMBP2
Clinical and molecular characteristics in three families with biallelic mutations in IGHMBP2
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DOI：
10.1016/j.nmd.2016.06.457
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发表时间：
2016-09-01
影响因子：
2.8
通讯作者：
Stromme, Petter
中科院分区：
文献类型：
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作者：
Pedurupillay, Christeen Ramane J.;Amundsen, Silja S.;Stromme, Petter
IGHMBP2基因的双等位基因突变可导致1型呼吸窘迫型脊髓性肌萎缩症（SMARD1）或2S型腓骨肌萎缩症（CMT2S）。我们报道了3个受IGHMBP2基因突变不同影响的家庭。患者1是一名8岁男孩，具有两种纯合变异：c.2T>C和c.861C>G，因感觉运动轴索神经病和慢性呼吸衰竭而需坐轮椅。患者2及其妹妹患者3具有复合杂合变异：c.983_987delAAGAA和c.1478C>T。然而，临床表型差异显著，4.5岁的哥哥患有感觉运动轴索神经病，但呼吸功能尚未受影响，而妹妹表现为婴儿型脊髓性肌萎缩症，并在11个月时因严重呼吸衰竭死亡。患者4是一名6岁女孩，IGHMBP2基因c.449 + 1G>T纯合突变，据记载可导致两种异常转录本，因轴索多发性神经病需依赖轮椅。患者1和3的临床表现与SMARD1一致，而患者2和4符合CMT2S。（C）2016作者。由爱思唯尔出版集团出版。
Biallelic mutations in IGHMBP2 cause spinal muscular atrophy with respiratory distress type 1 (SMARD1) or Charcot Marie Tooth type 2S (CMT2S). We report three families variably affected by IGHMBP2 mutations. Patient 1, an 8-year-old boy with two homozygous variants: c.2T>C and c.861C>G, was wheelchair bound due to sensorimotor axonal neuropathy and chronic respiratory failure. Patient 2 and his younger sister, Patient 3, had compound heterozygous variants: c.983_987delAAGAA and c.1478C>T. However, clinical phenotypes differed markedly as the elder with sensorimotor axonal neuropathy had still unaffected respiratory function at 4.5 years, whereas the younger presented as infantile spinal muscular atrophy and died from relentless respiratory failure at 11 months. Patient 4, a 6-year-old girl homozygous for IGHMBP2 c.449+1G>T documented to result in two aberrant transcripts, was wheelchair dependent due to axonal polyneuropathy. The clinical presentation in Patients 1 and 3 were consistent with SMARD1, whereas Patients 2 and 4 were in agreement with CMT2S. (C) 2016 The Authors. Published by Elsevier B.V.