Pasińska Magdalena, Łazarczyk Ewelina, Repczyńska Anna, Sobczyńska-Tomaszewska Agnieszka, Zimowski Janusz, Runge Agata, Haus Olga
Department of Clinical Genetics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.
Medical Center "Medgen", Warszawa, Poland.
Appl Clin Genet. 2022 May 14;15:27-38. doi: 10.2147/TACG.S357136. eCollection 2022.
The X and Y chromosomes are responsible for the determination and differentiation of the gonads, and their numerical and structural abnormalities may cause the abnormal development of secondary sex characteristics. The presence of abnormalities concerning X chromosome can also contribute to many genetically heterogeneous diseases associated with cognitive impairment and intellectual disability.
This study shows the effect of aberrations of the maternal X chromosome on the abnormal development of the child.
Ten women aged 26 to 40 years were consulted in genetic counselling clinic and subsequently subjected to cytogenetic and molecular tests due to abnormal psychomotor development of their children, in whom structural aberrations of the X chromosome had been detected.
Two women were diagnosed with changes in karyotype: 46,X,der(X)t(X;Y)(p22.3;q11.2) in one and 46,X,inv(X)(p21.2q13). Five women were diagnosed with microduplications in the short arm of the X chromosome; dupXp22.31 in one, and in four women dupXp22.33. The remaining three women were diagnosed with duplication in the long arm of the X chromosome; dupXq25 in one and dupXq26.3 in two women.
Genetic analysis of the X chromosome, based on cytogenetic and molecular methods of the highest available resolution, is extremely important in women with reproductive failure. These methods allow establishing accurately the breakpoints and rearrangements in chromosomes, and assessment of the copy number variation (CNV) can explain phenotypic variability with apparently similar aberrations. A more precise characterization of the alterations is necessary for the correct genetic diagnosis, as well as determination of the carrier status and genetic risk in family members.
X和Y染色体负责性腺的决定和分化，其数目和结构异常可能导致第二性征发育异常。X染色体异常的存在还可能导致许多与认知障碍和智力残疾相关的遗传异质性疾病。
本研究显示母源X染色体畸变对儿童异常发育的影响。
10名年龄在26至40岁之间的女性在遗传咨询门诊接受咨询，随后因其子女精神运动发育异常而接受细胞遗传学和分子检测，这些子女中检测到X染色体结构畸变。
两名女性被诊断为核型改变：一名为46,X,der(X)t(X;Y)(p22.3;q11.2)，另一名为46,X,inv(X)(p21.2q13)。五名女性被诊断为X染色体短臂微重复；一名为dupXp22.31，四名女性为dupXp22.33。其余三名女性被诊断为X染色体长臂重复；一名为dupXq25，两名女性为dupXq26.3。
基于最高分辨率的细胞遗传学和分子方法对X染色体进行遗传分析，对有生殖功能障碍的女性极为重要。这些方法能够准确确定染色体的断点和重排，对拷贝数变异（CNV）的评估可以解释明显相似畸变情况下的表型变异性。为了正确进行遗传诊断以及确定家庭成员的携带者状态和遗传风险，需要对这些改变进行更精确的特征描述。
