BACKGROUND: Loss-of-function mutations in the imprinted gene MKRN3 represent the most common known genetic defects associated with central precocious puberty (CPP). METHODS: We report the first case of a girl carrying an MKRN3 mutation detected in childhood and followed until the development of pubertal signs. RESULTS: The girl was screened at the age of 4 years because of a positive family history; her sister had developed CPP at 6 years of age and was found to harbor the MKRN3 p.Pro161Argfs*16 mutation, inherited from their asymptomatic father. During close follow-up, she initially developed increased growth velocity at 6 years (9 cm/year), followed by a slightly increased basal luteinizing hormone level (0.4 mIU/ml) and, ultimately, clinical thelarche with rapid progression (Tanner stage 1-3) between 6.3 and 6.7 years. In the context of a loss-of-function MKRN3 mutation and a positive family history, these features established the diagnosis of CPP and supported the initiation of treatment with a gonadotropin-releasing hormone analog. The absence of significant bone age advancement, pubic or axillary hair, or behavioral or social problems could be ascribed to the early diagnosis. CONCLUSION: The identification of carriers of MKRN3 mutations may contribute to early diagnosis of CPP, facilitating treatment decisions and guiding genetic counseling and prompt intervention in familial cases.
BACKGROUND: Loss-of-function mutations in the imprinted gene MKRN3 represent the most common known genetic defects associated with central precocious puberty (CPP). METHODS: We report the first case of a girl carrying an MKRN3 mutation detected in childhood and followed until the development of pubertal signs. RESULTS: The girl was screened at the age of 4 years because of a positive family history; her sister had developed CPP at 6 years of age and was found to harbor the MKRN3p.Pro161Argfs*16 mutation, inherited from their asymptomatic father. During close follow-up, she initially developed increased growth velocity at 6 years (9 cm/year), followed by a slightly increased basal luteinizing hormone level (0.4 mIU/ml) and, ultimately, clinical thelarche with rapid progression (Tanner stage 1-3) between 6.3 and 6.7 years. In the context of a loss-of-function MKRN3 mutation and a positive family history, these features established the diagnosis of CPP and supported the initiation of treatment with a gonadotropin-releasing hormone analog. The absence of significant bone age advancement, pubic or axillary hair, or behavioral or social problems could be ascribed to the early diagnosis. CONCLUSION: The identification of carriers of MKRN3 mutations may contribute to early diagnosis of CPP, facilitating treatment decisions and guiding genetic counseling and prompt intervention in familial cases.
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Authors: Arlene J George; Bin Dong; Hannah Lail; Morgan Gomez; Yarely C Hoffiz; Christopher B Ware; Ning Fang; Anne Z Murphy; Erik Hrabovszky; Desiree Wanders; Angela M Mabb Journal: iScience Date: 2022-05-10
Authors: Vassos Neocleous; Pavlos Fanis; Meropi Toumba; Barbara Gorka; Ioanna Kousiappa; George A Tanteles; Michalis Iasonides; Nicolas C Nicolaides; Yiolanda P Christou; Kyriaki Michailidou; Stella Nicolaou; Savvas S Papacostas; Athanasios Christoforidis; Andreas Kyriakou; Dimitrios Vlachakis; Nicos Skordis; Leonidas A Phylactou Journal: Front Endocrinol (Lausanne) Date: 2021-09-24 Impact factor: 5.555