Fusco Francesca, Conte Matilde Immacolata, Diociaiuti Andrea, Bigoni Stefania, Branda Maria Francesca, Ferlini Alessandra, El Hachem Maya, Ursini Matilde Valeria
Institute of Genetics and Biophysics "Adriano Buzzati-Traverso," IGB-CNR, Naples, Italy.
Dermatology Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy; and.
Pediatrics. 2017 Sep;140(3). doi: 10.1542/peds.2016-2950. Epub 2017 Aug 9.
Incontinentia pigmenti (IP; Online Mendelian Inheritance in Man catalog #308300) is an X-linked dominant ectodermal disorder caused by mutations of the inhibitor of κ polypeptide gene enchancer in B cells, kinase γ ()/ nuclear factor κB, essential modulator () gene. Hemizygous loss-of-function (LoF) mutations are lethal in males, thus patients are female, and the disease is always transmitted from an IP-affected mother to her daughter. We present 2 families with father-to-daughter transmission of IP and provide for the first time molecular evidence that the combination of somatic and germ-line mosaicism for loss of function mutations in IP males resulted in the transmission of the disease to a female child. We searched for the mutant allele in blood, urine, skin, and sperm DNA and found that the 2 fathers were somatic and germ-line mosaics for the p.Gln132×mutation or the exon 4-10 deletion of , respectively. The highest level of mutant cells was detected in the sperm, which might explain the recurrence of the disease. We therefore recommend careful clinical evaluation in IP male cases and the genetic investigation in sperm DNA to ensure correct genetic counseling and prevent the risk of paternal transmission of IP.
色素失禁症（IP；《人类孟德尔遗传在线》目录编号#308300）是一种X连锁显性外胚层疾病，由B细胞中κ多肽基因增强子抑制剂、激酶γ（）/核因子κB、必需调节因子（）基因突变引起。半合子功能丧失（LoF）突变在男性中是致命的，因此患者均为女性，且该疾病总是由患色素失禁症的母亲传给女儿。我们报告了2个色素失禁症父女相传的家系，并首次提供了分子证据，证明色素失禁症男性中功能丧失突变的体细胞和生殖系嵌合体组合导致了疾病传给女性后代。我们在血液、尿液、皮肤和精子DNA中寻找突变等位基因，发现两位父亲分别是p.Gln132×突变或外显子4 - 10缺失的体细胞和生殖系嵌合体。在精子中检测到的突变细胞水平最高，这可能解释了疾病的复发。因此我们建议对色素失禁症男性病例进行仔细的临床评估，并对精子DNA进行基因检测，以确保正确的遗传咨询并防止色素失禁症父系遗传的风险。
