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Case Reports
. 2014 Jan;22(1):136-9.
doi: 10.1038/ejhg.2013.56. Epub 2013 Apr 10.

Somatic mosaicism in trichorhinophalangeal syndrome: a lesson for genetic counseling

Carole Corsini  1 , Martin Gencik  2 , Marjolaine Willems  1 , Eva Decker  2 , Elodie Sanchez  3 , Jacques Puechberty  4 , Anouck Schneider  4 , Manon Girard  4 , Patrick Edery  5 , Patricia Bretonnes  5 , Jérôme Cottalorda  6 , Geneviève Lefort  4 , Claire Jeandel  7 , Pierre Sarda  1 , David Genevieve  3
Affiliations
Case Reports

Somatic mosaicism in trichorhinophalangeal syndrome: a lesson for genetic counseling

Carole Corsini et al. Eur J Hum Genet. 2014 Jan.

Abstract

Trichorhinophalangeal syndrome type I (TRPSI) is a genetic disorder characterized by sparse hair, a bulbous nasal tip, short stature with severe generalized shortening of all phalanges, metacarpal and metatarsal bones and cone-shaped epiphyses. This syndrome is caused by autosomal dominant mutations in the TRPS1 gene. However, because recurrence has been observed in siblings from healthy parents, an autosomal recessive mode of inheritance has also been suggested. We report on a male patient, born to healthy unrelated parents, with TRPSI. Using Sanger sequencing, we identified a mutation in the TRPS1 gene (c.2735 G>A, P.Cys912Tyr). The same mutation was detected as a 10% mosaic mutation by Pyrosequencing in blood-derived DNA from his healthy mother. To our knowledge, this is the first time that somatic mosaicism has been identified in TRPSI. This data combined with the observations of recurrences in siblings from healthy parents modifies the genetic counseling for TRPSI, which should discuss a 5-10 percent recurrence risk for healthy parents with an affected child because of the possibility of germinal mosaicism.

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Figures

Figure 1
Figure 1
Clinical and radiological features in the patient and his mother. Note (a) and (b) brachydactyly, shortening of all phalanges (hands and feet) and fingers deviated at proximal interphalangeal joints, (c) femoral epiphyseal dysplasia, (d) cone-shaped epiphyses and carpal bone age delay (carpal bone age at 3 years for a chronological age of 5 years and 2 months) in the patient, and (e) normal hands, (f) normal femoral heads (g) and normal hands on the X-rays of the mother.
Figure 2
Figure 2
Molecular data from the patient and the healthy parents. Note (a) the heterozygous mutation c.2735G>A (P.Cys912Tyr) in exon 6 of the TRPS1 gene on the electropherogram and NGS data of the patient, (b) the familial mutation was not detected in the healthy father, (c) in the healthy mother, the c.2735 G>A (P.Cys912Tyr) somatic mutation can be seen on the electropherogram and NGS data—note the mosaicism estimated at ∼10%.
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