Abstract:

A 26-year-old woman with psychomotor developmental delay since late infancy showed rapid deterioration of her psychomotor abilities at the 11 years of age. She had gained the ability to verbally express herself and perform motor activities such as running and dancing in early childhood, but she lost the ability to verbally communicate and was unable to walk independently after this period. She also presented with dystonia in the right extremities, which markedly fluctuated with a periodicity of hours to months. Sleep disturbance and epileptic seizures also emerged during adolescence. Frontal lobe atrophy and hypoperfusion of the left cerebral hemisphere were noted on neuroimaging examinations. Analysis of the MECP2 gene revealed a late truncating mutation of c.1196_1200delCCACC (p.P399QfsX4) near the 3'-terminal of the coding region. The phenotype of this patient corresponds to the rare, unestablished variant of "late childhood deterioration" in MECP2-related disorders. For the first time, MECP2 mutation was confirmed to be the genetic basis of this condition.

日本語要旨:

常染色体劣性遺伝である肢体型筋ジストロフィー(LGMD2D)の症例は民族的な背景により様々であり、アジアにおいては数例のみ報告がある。原因遺伝子としてSGCAが知られており、本研究においては5人の患者にSGCA新規ホモザイガス変異c.101G>T(p.Arg34Leu)を、また、両親にはヘテロザイガス変異を見出した。さらにハプロタイプ解析から、台湾の大先住民家系に属するこれら5人の患者とその両親は共通のハプロタイプであった。このことは、台湾、殊に大先住民族家系におけるSGCA c.101G>T変異の罹患率調査の重要性を示唆する結果となった。