Vertical transmission of a large calvarial ossification defect due to heterozygous variants of ALX4 and TWIST1.
Vertical transmission of a large calvarial ossification defect due to heterozygous variants of ALX4 and TWIST1.
复制标题
ALX4 和 TWIST1 杂合变异导致大颅骨骨化缺损的垂直传播。
DOI：
10.1002/ajmg.a.62036
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Lalani,SeemaR
中科院分区：
文献类型：
--
作者：
Walters,MichelleE;Lacassie,Yves;Azamian,Mahshid;Franciskovich,Rachel;Zapata,Gladys;Hernandez,PatriciaP;Liu,Pengfei;Campbell,IanM;Bostwick,BretL;Lalani,SeemaR
ALX4is a homeobox gene expressed in the mesenchyme of developing bone and is known to play an important role in the regulation of osteogenesis. Enlarged parietal foramina (EPF) is a phenotype of delayed intramembranous ossification of calvarial bones due to variants ofALX4. The contrasting phenotype of premature ossification of sutures is observed with heterozygous loss‐of‐function variants ofTWIST1, which is an important regulator of osteoblast differentiation. Here, we describe an individual with a large cranium defect, with dominant transmission from the mother, both carrying disease causing heterozygous variants inALX4andTWIST1. The distinct phenotype of absent superior and posterior calvarium in the child and his mother was in sharp contrast to the other affected maternal relatives with a recognizableALX4‐related EPF phenotype. This report demonstrates comorbid disorders of Saethre‐Chotzen syndrome and EPF in a mother and her child, resulting in severe skull defects reminiscent of calvarial abnormalities observed with bilallelicALX4variants. To our knowledge this is the first instance ofALX4andTWIST1variants acting synergistically to cause a unique phenotype influencing skull ossification.
