Volodarsky Michael, Zilberman Uri, Birk Ohad S
The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
Pediatric Dental Unit, Barzilai Medical Center, Ashkelon, Israel.
Arch Oral Biol. 2015 Jun;60(6):919-22. doi: 10.1016/j.archoralbio.2015.02.018. Epub 2015 Feb 28.
To relate the peculiar phenotype of amelogenesis imperfecta in a large Bedouin family to the genotype determined by whole genome linkage analysis.
Amelogenesis imperfecta (AI) is a broad group of inherited pathologies affecting enamel formation, characterized by variability in phenotypes, causing mutations and modes of inheritance. Autosomal recessive or compound heterozygous mutations in FAM20A, encoding sequence similarity 20, member A, have been shown to cause several AI phenotypes. Five members from a large consanguineous Bedouin family presented with hypoplastic amelogenesis imperfecta with unerupted and resorbed permanent molars. Following Soroka Medical Center IRB approval and informed consent, blood samples were obtained from six affected offspring, five obligatory carriers and two unaffected siblings. Whole genome linkage analysis was performed followed by Sanger sequencing of FAM20A.
The sequencing unravelled a novel homozygous deletion mutation in exon 11 (c.1523delC), predicted to insert a premature stop codon (p.Thr508Lysfs*6).
We provide an interesting case of novel mutation in this rare disorder, in which the affected kindred is unique in the large number of family members sharing a similar phenotype.
将一个大型贝都因家族中牙釉质发育不全的特殊表型与通过全基因组连锁分析确定的基因型相关联。
牙釉质发育不全（AI）是一组广泛的遗传性疾病，影响牙釉质形成，其特征在于表型的变异性，导致突变和遗传方式。编码序列相似性20成员A的FAM20A中的常染色体隐性或复合杂合突变已被证明可导致多种AI表型。一个大型近亲贝都因家族的五名成员表现为发育不全性牙釉质发育不全，伴有未萌出和吸收的恒磨牙。在获得索罗卡医疗中心机构审查委员会批准和知情同意后，从六名受影响的后代、五名 obligatory 携带者和两名未受影响的兄弟姐妹采集了血样。进行全基因组连锁分析，随后对FAM20A进行桑格测序。
测序揭示了外显子11中的一个新的纯合缺失突变（c.1523delC），预计会插入一个过早的终止密码子（p.Thr508Lysfs*6）。
我们提供了一个在这种罕见疾病中发现新突变的有趣案例，其中受影响的亲属在具有相似表型的家庭成员数量上是独特的。
