Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: A case of gonadal mosaicism. Issue 9 (28th May 2014)

• Record Type: Journal Article
• Authors: Dhamija, Radhika; Kirmani, Salman; Wang, Xiangling; Ferber, Matthew J.; Wieben, Eric D.; Lazaridis, Konstantinos N.; Babovic‐Vuksanovic, Dusica
• Is Part Of: American journal of medical genetics. Volume 164:Issue 9(2014.)
• Page Start: 2356
• Page End: 2359
• Publication Date: 2014-05-28
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36621
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36621-sec-0001" sec-type="section"> <p>Hartsfield syndrome has been recently reported to be associated with mutations in <italic>FGFR1</italic> however, to this date; no familial cases have been reported. In this report, we describe two siblings with Hartsfield syndrome and a novel de novo <italic>FGFR1</italic> mutation suggesting gonadal mosaicism. The proband presented at our institution at age 6 years with a clinical diagnosis of Hartsfield syndrome and requesting further genetic evaluation. Previous studies included a normal karyotype, oligonucleotide array, and single gene testing for nonsyndromic holoprosencephaly (<italic>SHH</italic>, <italic>SIX3</italic>, <italic>ZIC2</italic>, <italic>TGIF</italic>). At the age of 6 years, exome sequencing was performed and a de novo novel missense variant was identified in <italic>FGFR1</italic> (coding for fibroblast growth factor‐1) on chromosome 8p12: c.1880G>C (p.R627T). Subsequently, a younger sibling was born with the same phenotype (holoprosencephaly, ectrodactyly of bilateral hands and feet and bilateral cleft lip and palate). Targeted sequencing of <italic>FGFR1</italic> revealed the identical variant that was previously identified in the proband. To our knowledge this observation is the first documentation of familial recurrence of Hartsfield syndrome. As both parents were negative for the sequence variant in <italic>FGFR1</italic> gene by testing peripheral blood samples, this suggests gonadal mosaicism. The frequency of gonadal mosaicism in Hartsfield syndrome is not known however given our case, this possibility should be taken in to consideration for recurrence risk estimation in children of clinically unaffected parents. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>