Variable expressivity of the phenotype in two families with brachydactyly type E, craniofacial dysmorphism, short stature and delayed bone age caused by novel heterozygous mutations in the PTHLH gene

Journal of Human Genetics
Aleksander JamsheerAnna Latos-Bieleńska

Abstract

Brachydactyly refers to shortening of digits due to hypoplasia or aplasia of bones forming the hands and/or feet. Isolated brachydactyly type E (BDE), which is characterized by shortened metacarpals and/or metatarsals, results in a small proportion of patients from HOXD13 or PTHLH mutations, although in the majority of cases molecular lesion remains unknown. BDE, like other brachydactylies, shows clinical heterogeneity with highly variable intrafamilial and interindividual expressivity. In this study, we investigated two Polish cases (one familial and one sporadic) presenting with BDE and additional symptoms due to novel PTHLH mutations. Apart from BDE, the affected family showed short stature, mild craniofacial dysmorphism and delayed bone age. Sanger sequencing of PTHLH revealed a novel heterozygous frameshift mutation c.258delC(p.N87Tfs*18) in two affected individuals and one relative manifesting mild brachydactyly. The sporadic patient, in addition to BDE, presented with craniofacial dysmorphism, normal stature and bone age, and was demonstrated to carry a de novo heterozygous c.166C>T(p.R56*) mutation. Our paper reports on the two novel truncating PTHLH variants, resulting in variable combination of BDE and other symptoms....Continue Reading

References

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Citations

Feb 18, 2017·American Journal of Medical Genetics. Part a·Arrate PeredaGuiomar Perez de Nanclares
Mar 4, 2018·BMC Medical Genetics·Arrate PeredaGuiomar Perez de Nanclares
Nov 21, 2018·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Monica ReyesHarald Jüppner
Jul 1, 2018·Nature Reviews. Endocrinology·Giovanna MantovaniAgnès Linglart
Dec 21, 2019·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Monica ReyesHarald Jüppner

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