保存恩典|概述
Addison Lennon met all her early milestones: she sat up on time, crawled on time and walked on time. At about 4 months, however, she had a seizure, and her parents started to worry. By 9 months, her head appeared small for her age.
Her neurologist reassured the family that Addison could still be within the lowest 5 percent of the normal range. “We were thinking she was typical,” says Kari Lennon, “she would be in that 5 percent.”
At 15 months, however, Addison had another seizure that was a lot more severe. She had been tested for everything. No one could pinpoint the cause of her so-called microcephaly, or small head.
卡里在网上花了无数小时来寻找答案。“我如何解决addie？我怎么能让她变得更好？”
Reassured that Addison’s condition was likely caused by a virus her mother had contracted during pregnancy, the Lennons went on to have three boys, Sam, Jack and Brooks.
A new brother: Brooks
Shortly after his arrival, the Lennons knew that Brooks had the same disease as his sister. His head was small and as he grew, he too fell below the normal range. Could there be a genetic cause?
Kari remembered, from one of her late-night Internet searches, a clinic at Children’s Hospital Boston that specialized in hereditary forms of microcephaly. The clinic team, led by Christopher Walsh, MD, PhD, and which included Edward Gilmore, MD, examined the children. Addison and Brooks did not have any known heritable brain disease.
“Ed and I looked at each other and said, ‘maybe these children have Microcephaly with Seizures,’” recalls Walsh.
Discovered two years earlier by the Walsh team, Microcephaly with Seizures, or MCSZ, is an extremely unusual form of microcephaly in which the brain is of smaller size but is otherwise structurally normal. People with MCSZ have seizures, but typically many more than Addison and Brooks were experiencing. The team therefore suspected that the children had a mild form of MCSZ. The disease, however, had never been seen outside of the Middle East.
该小组并没有避免，对儿童的PNKP基因进行了测序，MCSZ的关键基因改变了。艾迪生（Addison）和布鲁克斯（Brooks）都在基因的两个副本中都有突变。但是这些突变之一以前从未见过，由于它没有消除基因的功能，因此该团队根本无法确定Addison和Brooks拥有MCSZ。
The phone call
布鲁克斯的病情恶化了。他的癫痫发作不受控制。他每隔一周就在重症监护中。在混乱中，列侬得知他们正在期待另一个孩子。
列侬发现自己进入了22个。有意，将另一个孩子带入这种遗传状况对他们来说是不可想象的。但是，除非他们确定未来的孩子会患上这种疾病，否则他们不会终止怀孕。
卡里（Kari）的产科医生敦促家庭再与沃尔什（Walsh）团队伸出一段时间。也许他们已经确定了孩子小头畸形的原因。卡里回忆说：“我丈夫与她见面后，从汽车上发送了一封电子邮件。”“第二天早上，我们从布伦达·巴里（Brenda Barry）回到了沃尔什（Walsh）实验室，要求那天晚上与我们交谈，因为他们确实有新闻可以与我们分享。”
Just weeks before, the team had completed biochemical studies on cells derived from Addison and Brooks, and they now had evidence confirming that the two had MCSZ. Eleven weeks into Kari’s pregnancy, the growing fetus was tested and found to be free of the MCSZ mutations its siblings had.
列侬的MCSZ如此罕见，只能通过研究世界另一端具有共同血统的大家庭才能检测到。艾迪生和布鲁克斯各自携带的两个MCSZ突变之一以前是在沃尔什实验室对中东家庭的研究中发现的。
“We never would have found this gene in the U.S.,” says Walsh. “We needed to go over to the Middle East to make a difference here.”
Amazing Grace
The day the Lennons’ new baby was born, they sent an email to the Boston Children’s clinic, announcing that she would be named Grace Gilmore, in part for the neurologist on the Walsh team, and expressing their gratitude for a healthy baby.
“I cannot remember a better day since I became a doctor,” says Walsh. “For a geneticist, this is as good as it gets.”
And Kari Lennon, knowing what is behind her children’s condition, can finally sleep at night. “We are so lucky,” she says. “They have just given us the biggest gifts in the world. A diagnosis for Addison and Brooks and a baby that is healthy.”