What question did this study set out to answer?

To investigate whether mutations in FGF10 are responsible for LADD syndrome.

March 30, 2006Clinical Genetics140 citationsOpen Access

LADD syndrome is caused byFGF10mutations

JMJM MilunskyBoston University GZGeping ZhaoSema4 (United States)TMThomas A. MaherPennsylvania State University

Key Points

To investigate whether mutations in FGF10 are responsible for LADD syndrome.
Analysis of genetic mutations in families with reported cases of LADD syndrome and ALSG.
Identification of a de novo missense mutation in a child and a nonsense mutation in a mother and daughter duo.
Comparison to previous findings in FGF10 mutant mice.
Identified a de novo missense mutation in FGF10 in a 3-year-old LADD syndrome patient.
Detected a nonsense mutation in a mother and daughter, with the daughter diagnosed with LADD syndrome.
Confirmed findings align with previous studies indicating FGF10 mutations produce compatible phenotypes.

Abstract

Lacrimo-auriculo-dento-digital syndrome LADD (MIM 149730) is an autosomal-dominant multiple congenital anomaly disorder characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems, cup-shaped ears, hearing loss, and dental and digital anomalies. Loss of function mutations in FGF10 were recently described in aplasia of the lacrimal and salivary glands ALSG (MIM 180920; MIM 103420) (Entesarian et al., Nat Genet 2005: 37: 125-127, Milunsky et al., American College of Medical Genetics Annual Meeting, Dallas, TX, 2005: A100). Due to the significant phenotypic overlap between LADD syndrome and ALSG and the variable expressivity of both the disorders, we hypothesized that FGF10 mutations could also result in LADD syndrome. A de novo missense mutation was found in exon 3 of FGF10 in a 3-year-old female (Family 1) with LADD syndrome. This missense mutation, resulting in a non-conservative amino acid change, was confirmed by restriction enzyme digestion and was not found in 500 control chromosomes. A nonsense mutation was also found in exon 2 of FGF10 (Family 2) in a 19-year-old mother with ALSG and her 2-year-old daughter with LADD syndrome. Previous studies of FGF10 mutant mice have demonstrated abnormalities consistent with ALSG and LADD syndrome. We conclude that ALSG and LADD syndrome may represent variable presentations of the same clinical spectrum caused by FGF10 mutations.

Ask AI

Helpful

Bookmark

View Full Paper