Köhler J, Rupilius B, Otto M, Bathke K, Koch M C
Medizinisches Zentrum für Humangenetik der Philipps-Universität Marburg, Germany.
Hum Genet. 1996 Oct;98(4):485-90. doi: 10.1007/s004390050244.
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominantly inherited neuromuscular disorder affecting facial and shoulder girdle muscles with subsequent progression to the pelvic girdle and lower extremities. The major gene involved has been localized to chromosome 4q35 (FSHD1A). The 4q35 DNA marker p13E-11 (D4F104S1) detects a de novo EcoRI DNA rearrangement of < 30 kb in isolated and familial cases. The intrafamilial size of the fragment is constant, inversely correlated with the severity, and directly correlated with the age of onset of the condition. There has been evidence of parental mosaicism in FSHD1A for the D4F104S1 locus. Four female and three male clinically unaffected parents have been described to be carriers of EcoRI fragments of the same size as their affected offspring, but with a markedly less intensive hybridization signal (semi-quantitative evidence). In our total sample of 42 FSHD1A families, we found semi-quantitative evidence of parental D4F104S1 mosaicism in 11 families (EcoRI fragment size range: 12-27 kb). On analysis with adjacent 4q35 probes (D4S163, D4S139), additional qualitative evidence of germline mosaicism could be obtained in two families. In our mosaic families and in the families reported in the literature, a female predominance of mosaicism carriers (13 females versus 5 males) could be noted. In our sample, mosaicism was observed in multigeneration families, in families with isolated cases, and in families with two and three affected children from seemingly unaffected parents. A short EcoRI fragment once having emerged in a mosaicism carrier was found to be transmitted autosomal dominantly to subsequent generations. Of all reported sporadic patients, 19% have a mosaic parent. Finding evidence of parental mosaicism in all our families with more than one affected child of seemingly unaffected parents suggests that there is no autosomal recessively inherited form of FSHD1A.
面肩肱型肌营养不良症（FSHD）是一种常染色体显性遗传的神经肌肉疾病，影响面部和肩胛带肌肉，随后发展至骨盆带和下肢。主要相关基因已定位到4号染色体长臂3区5带（FSHD1A）。4q35 DNA标记p13E - 11（D4F104S1）在散发和家族性病例中可检测到小于30 kb的从头EcoRI DNA重排。片段的家族内大小恒定，与严重程度呈负相关，与疾病的发病年龄呈正相关。有证据表明FSHD1A中D4F104S1位点存在亲本嵌合体。已描述4名临床未受影响的女性和3名男性父母为EcoRI片段携带者，其片段大小与受影响后代相同，但杂交信号强度明显较低（半定量证据）。在我们总共42个FSHD1A家族的样本中，我们在11个家族中发现了亲本D4F104S1嵌合体的半定量证据（EcoRI片段大小范围：12 - 27 kb）。用相邻的4q35探针（D4S163、D4S139）分析时，在两个家族中可获得生殖系嵌合体的更多定性证据。在我们的嵌合家族以及文献报道的家族中，可以注意到嵌合体携带者以女性为主（13名女性对5名男性）。在我们的样本中，在多代家族、散发病例家族以及看似未受影响的父母有两名和三名患病子女的家族中均观察到嵌合体。发现嵌合体携带者中一旦出现短EcoRI片段，会以常染色体显性方式传递给后代。在所有报道的散发病例中，19%有嵌合亲本。在我们所有看似未受影响的父母有不止一名患病子女的家族中都发现了亲本嵌合体的证据，这表明不存在FSHD1A的常染色体隐性遗传形式。
