BACKGROUND: Congenital hypothyroidism (CH) is a common endocrine disorder in newborns. The cause of CH is thyroid dysgenesis in 80-85% of patients. Paired box gene 8 (PAX8) is a thyroid transcription factor that plays an important role in thyroid organogenesis and development. To date, 22 different PAX8 gene mutations have been reported. METHODS: Four generations of a Hungarian Jewish family were affected, and in the 3 generations studied, 9 males and 4 females were affected and 3 first-degree relatives were unaffected. Six were diagnosed at birth [thyroid-stimulating hormone (TSH) level 59-442 mU/l] and 7 at 2-48 years of age (TSH level 6-223 mU/l). One affected patient had thyroid hemiagenesis on ultrasound. RESULTS: Direct sequencing of the PAX8 gene revealed a novel single nucleotide substitution (c.162 A>T) in exon 2 that resulted in the substitution of the normal serine 54 with a cysteine (S54C), which segregated with elevated serum TSH levels. Other mutations of the same amino acid (S54G and S54R) have also been shown to produce functional impairment. CONCLUSION: We report a large family with a novel mutation in the PAX8 gene presenting with variable phenotype and with a high proportion of affected family members.
BACKGROUND:Congenital hypothyroidism (CH) is a common endocrine disorder in newborns. The cause of CH is thyroid dysgenesis in 80-85% of patients. Paired box gene 8 (PAX8) is a thyroid transcription factor that plays an important role in thyroid organogenesis and development. To date, 22 different PAX8 gene mutations have been reported. METHODS: Four generations of a Hungarian Jewish family were affected, and in the 3 generations studied, 9 males and 4 females were affected and 3 first-degree relatives were unaffected. Six were diagnosed at birth [thyroid-stimulating hormone (TSH) level 59-442 mU/l] and 7 at 2-48 years of age (TSH level 6-223 mU/l). One affected patient had thyroid hemiagenesis on ultrasound. RESULTS: Direct sequencing of the PAX8 gene revealed a novel single nucleotide substitution (c.162 A>T) in exon 2 that resulted in the substitution of the normal serine 54 with a cysteine (S54C), which segregated with elevated serum TSH levels. Other mutations of the same amino acid (S54G and S54R) have also been shown to produce functional impairment. CONCLUSION: We report a large family with a novel mutation in the PAX8 gene presenting with variable phenotype and with a high proportion of affected family members.
Authors: Pina Marotta; Elena Amendola; Marzia Scarfò; Pasquale De Luca; Pietro Zoppoli; Angela Amoresano; Mario De Felice; Roberto Di Lauro Journal: Mol Cell Endocrinol Date: 2014-08-12 Impact factor: 4.102
Authors: Pia Hermanns; Scott Shepherd; Mohamed Mansor; John Schulga; Jez Jones; Malcolm Donaldson; Joachim Pohlenz Journal: Thyroid Date: 2014-03-21 Impact factor: 6.568
Authors: I C Nettore; S Desiderio; E De Nisco; V Cacace; L Albano; N Improda; P Ungaro; M Salerno; A Colao; P E Macchia Journal: J Endocrinol Invest Date: 2017-11-20 Impact factor: 4.256