Jorge Alexander A L, Souza Silvia C, Nishi Miriam Y, Billerbeck Ana E, Libório Débora C C, Kim Chong A, Arnhold Ivo J P, Mendonca Berenice B
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas, SP, Brazil.
Clin Endocrinol (Oxf). 2007 Jan;66(1):130-5. doi: 10.1111/j.1365-2265.2006.02698.x.
The frequency of SHOX mutations in children with idiopathic short stature (ISS) has been found to be variable. We analysed the SHOX gene in children with ISS and Leri-Weill dyschondrosteosis (LWD) and evaluated the phenotypic variability in patients harbouring SHOX mutations.
Sixty-three ISS, nine LWD children and 21 affected relatives.
SHOX gene deletion was evaluated by fluorescence in situ hybridization (FISH), Southern blotting and segregation study of polymorphic marker. Point mutations were assessed by direct DNA sequencing.
None of the ISS patients presented SHOX deletions, but two (3.2%) presented heterozygous point mutations, including the novel R147H mutation. However, when ISS patients were selected by sitting height : height ratio (SH/H) for age > 2 SD, mutation frequency detection increased to 22%. Eight (89%) LWD patients had SHOX deletions, but none had point mutations. Analysis of the other relatives in the families carrying SHOX mutations identified 14 children and 17 adult patients. A broad phenotypic variability was observed in all families regarding short stature severity and Madelung deformities. However, the presence of disproportional height, assessed by SH/H, was observed in all children and 82% of adult patients, being the most common feature in our patients with SHOX mutations.
Patients with SHOX mutations present a broad phenotypic variability. SHOX mutations are very frequent in LWD (89%), in opposition to ISS (3.2%) in our cohort. The use of SH/H SDS as a selection criterion increases the frequency of SHOX mutation detection to 22% and should be used for selecting ISS children to undergo SHOX mutation molecular studies.
已发现特发性矮小（ISS）儿童中SHOX突变的频率存在差异。我们分析了ISS和Leri-Weill软骨发育不全（LWD）儿童的SHOX基因，并评估了携带SHOX突变患者的表型变异性。
63例ISS患儿、9例LWD患儿及21例受累亲属。
通过荧光原位杂交（FISH）、Southern印迹法及多态性标记的分离研究评估SHOX基因缺失。通过直接DNA测序评估点突变。
ISS患者均未出现SHOX基因缺失，但有2例（3.2%）出现杂合点突变，包括新的R147H突变。然而，当根据年龄的坐高与身高比值（SH/H）＞2标准差来选择ISS患者时，突变频率检测增加到22%。8例（89%）LWD患者存在SHOX基因缺失，但均无点突变。对携带SHOX突变家庭中的其他亲属进行分析，确定了14名儿童和17名成年患者。在所有家庭中，观察到身材矮小严重程度和马德隆畸形方面存在广泛的表型变异性。然而，通过SH/H评估的身高不成比例在所有儿童和82%的成年患者中均有观察到，是我们SHOX突变患者中最常见的特征。
SHOX突变患者表现出广泛的表型变异性。在我们的队列中，SHOX突变在LWD中非常常见（89%），而在ISS中则较少见（3.2%）。使用SH/H SDS作为选择标准可将SHOX突变检测频率提高到22%，应将其用于选择ISS儿童进行SHOX突变分子研究。
