Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: A case of gonadal mosaicism

Radhika Dhamija, Salman Kirmani, Xiangling Wang, Matthew J. Ferber, Eric D Wieben, Konstantinos N Lazaridis, Dusica Babovic-Vuksanovic

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Hartsfield syndrome has been recently reported to be associated with mutations in FGFR1 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 FGFR1 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 (SHH, SIX3, ZIC2, TGIF). At the age of 6 years, exome sequencing was performed and a de novo novel missense variant was identified in FGFR1 (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 FGFR1 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 FGFR1 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.

Original languageEnglish (US)
Pages (from-to)2356-2359
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Volume164
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Fibroblast Growth Factor 1
Mosaicism
Siblings
Mutation
Parents
Holoprosencephaly
Exome
Recurrence
Cleft Lip
Cleft Palate
Oligonucleotide Array Sequence Analysis
Karyotype
Documentation
Genes
Foot
Hand
Chromosomes
Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip-Palate
Phenotype

Keywords

  • FGFR1 mutation
  • Gonadal mosaicism
  • Hartsfield syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome : A case of gonadal mosaicism. / Dhamija, Radhika; Kirmani, Salman; Wang, Xiangling; Ferber, Matthew J.; Wieben, Eric D; Lazaridis, Konstantinos N; Babovic-Vuksanovic, Dusica.

In: American Journal of Medical Genetics, Part A, Vol. 164, No. 9, 2014, p. 2356-2359.

Research output: Contribution to journalArticle

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